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9. Elevation of Arginase-II in Podocytes Contributes to Age-Associated Albuminuria in Male Mice.

Author

Ajalbert, Guillaume, Brenna, Andrea, Ming, Xiu-Fen, Yang, Zhihong, and Potenza, Duilio M.

Subjects
MICE, KNOCKOUT mice, ALBUMINURIA, CHRONIC kidney failure, KIDNEY diseases, MALES
Abstract

One of the manifestations of renal aging is podocyte dysfunction and loss, which are associated with proteinuria and glomerulosclerosis. Studies show a male bias in glomerular dysfunction and chronic kidney diseases, and the underlying mechanisms remain obscure. Recent studies demonstrate the role of an age-associated increase in arginase-II (Arg-II) in proximal tubules of both male and female mice. However, it is unclear whether Arg-II is also involved in aging glomeruli. The current study investigates the role of the sex-specific elevation of Arg-II in podocytes in age-associated increased albuminuria. Young (3–4 months) and old (20–22 months) male and female mice of wt and arginase-II knockout (arg-ii−/−) were used. Albuminuria was employed as a readout of glomerular function. Cellular localization and expression of Arg-II in glomeruli were analyzed using an immunofluorescence confocal microscope. A more pronounced age-associated increase in albuminuria was found in male than in female mice. An age-associated induction of Arg-II in glomeruli and podocytes (as demonstrated by co-localization of Arg-II with the podocyte marker synaptopodin) was also observed in males but not in females. Ablation of the arg-ii gene in mice significantly reduces age-associated albuminuria in males. Also, age-associated decreases in podocyte density and glomerulus hypertrophy are significantly prevented in male arg-ii−/− but not in female mice. However, age-associated glomerulosclerosis is not affected by arg-ii ablation in both sexes. These results demonstrate a role of Arg-II in sex-specific podocyte injury in aging. They may explain the sex-specific differences in the development of renal disease in humans during aging. [ABSTRACT FROM AUTHOR]

Published
2023
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14. The hexosamine biosynthesis inhibitor azaserine prevents endothelial inflammation and dysfunction under hyperglycemic condition through antioxidant effects

Author

Rajapakse, Angana Gupta, Ming, Xiu-Fen, Carvas, Joao M., and Yang, Zhihong

Subjects
Cell adhesion molecules -- Properties, Endothelium -- Properties, Hyperglycemia -- Development and progression, Carcinogens -- Properties, Cocarcinogens -- Properties, Biological sciences
Abstract

Hexosamine biosynthetic pathway (HBP) accounts for some cardiovascular adverse effects of hyperglycemia. We investigated whether the HBP inhibitor azaserine protects against hyperglycemia-induced endothelial damage dependently of HBP. Human endothelial cells isolated from umbilical veins were exposed either to a high (30.5 mmol/l) or low concentration of glucose (5.5 mmol/l) for 4 days, followed by a stimulation with TNF-[alpha] (1 ng/ml, 24 h). The blockade of the rate-limiting enzyme glutamine:fructose-6-phosphate amido-transferase inhibited HBP flux and oxidative stress (generation of superoxide and peroxynitrite) under the hyperglycemic condition and prevented the synergistic stimulation of VCAM-1 and ICAM-1 expression by hyperglycemia and TNF-[alpha]. In the cells cultured under a low-glucose condition when no increased HBP flux occurred, azaserine enhanced the manganese-superoxide dismutase (MnSOD) protein level and also inhibited the oxidative stress and the expression of VCAM-1 and ICAM-1 in response to TNF-[alpha]. Moreover, the polyphenol resveratrol inhibited the oxidative stress and adhesion molecule expression and did not decrease the HBP flux under the hyperglycemia condition. In addition, in isolated rat aortas exposed to hyperglycemic buffer for 5 h when no significant HBP flux occurred, azaserine upregulated the MnSOD protein level and prevented decreased endothelium-dependent relaxations to acetylcholine. In conclusion, hyperglycemia independently increases oxidative stress and HBP flux, amplifies endothelial inflammation, and impairs endothelial function mainly through oxidative stress and not the HBP pathway. Azaserine protects against hyperglycemic endothelial damage through its antioxidant effect independently of inhibiting HBP pathway. adhesion molecules; endothelium; glucose; O-linked acetylglusamine; superoxide

Published
2009

15. Detrimental Effects of Chronic L-Arginine Rich Food on Aging Kidney

Author

Huang, Ji, Ladeiras, Diogo, Yu, Yi, Ming, Xiu-Fen, and Yang, Zhihong

Subjects
Pharmacology, kidney, inflammation, aging, arginase, arginine supplementation, Original Research
Abstract

The impaired L-arginine/nitric oxide pathway is a well-recognized mechanism for cardiovascular and renal diseases with aging. Therefore, supplementation of L-arginine is widely proposed to boost health or as adjunct therapy for the patients. However, clinical data, show adverse effects and even enhanced mortality in patients receiving long-term L-arginine supplementation. The effects of long-term L-arginine supplementation on kidney aging and the underlying mechanisms remain elusive. Moreover, high protein and high amino acid diet has been thought detrimental for kidney. We therefore investigated effects of chronic dietary L-arginine supplementation on kidney aging. In both young (4 months) and old (18–24 months) mice, animals either receive standard chow containing 0.65% L-arginine or diet supplemented with L-arginine to 2.46% for 16 weeks. Inflammation and fibrosis markers and albuminuria are then analyzed. Age-associated increases in tnf-α, il-1β, and il-6, vcam-1, icam-1, mcp1, inos, and macrophage infiltration, collagen expression, and S6K1 activation are observed, which is not favorably affected, but rather further enhanced, by L-arginine supplementation. Importantly, L-arginine supplementation further enhances age-associated albuminuria and mortality particularly in females, accompanied by elevated renal arginase-II (Arg-II) levels. The enhanced albuminuria by L-arginine supplementation in aging is not protected in Arg-II−/− mice. In contrast, L-arginine supplementation increases ROS and decreases nitric oxide production in old mouse aortas, which is reduced in Arg-II−/− mice. The results do not support benefits of long-term L-arginine supplementation. It rather accelerates functional decline of kidney and vasculature in aging. Thus, the long-term dietary L-arginine supplementation should be avoided particularly in elderly population.

Published
2021

16. Inhibition of p38mapk reduces adipose tissue inflammation in aging mediated by arginase-II

Author

Huang, Ji, Liu, Chang, Ming, Xiu-Fen, Yang, Zhihong, Huang, Ji, Liu, Chang, Ming, Xiu-Fen, and Yang, Zhihong

Abstract

Background: Adipose tissue inflammation occurs not only in obesity but also in aging and is mechanistically linked with age-associated diseases. Studies show that ablation of the l-arginine-metabolizing enzyme arginase-II (Arg-II) reduces adipose tissue inflammation and improves glucose tolerance in obesity. However, the role of Arg-II in aging adipose tissue inflammation is not clear. Objective: This study investigated the role of Arg-II in age-associated adipose tissue inflammation. Methods: Visceral adipose tissues of young (3–6 months) and old (20–24 months) wild-type (WT) and Arg-II−/− mice were investigated. Immunofluorescence confocal microscopy was performed for analysis of macrophage accumulation and cellular localization of arginase and cytokines; expression of arginase and cytokines was analyzed by qRT-PCR or immunoblotting or ELISA; activation of mitogen-activated protein kinases in adipose tissues was analyzed by immunoblotting; and arginase activity was measured by colorimetric determination of urea production. Results: In the old WT mice, there is more macrophage accumulation in the visceral adipose tissues than in Arg-II knockout animals. An age-associated increase in arginase activity and Arg-II expression in adipose tissues of WT mice is observed. Arg-II knockout enhances Arg-I expression and activity, but inhibits interleukin (IL)-6 expression and secretion and reduces active p38mapk in aging adipose tissue macrophages and stromal cells. Treatment of aging adipose tissues of WT mice with a specific p38mapk inhibitor SB203580 reduces IL-6 secretion. Conclusions: Arg-II promotes IL-6 production in aging adipose tissues through p38mapk. The results suggest that targeting Arg-II or inhibiting p38mapk could be beneficial in reducing age-associated adipose tissue inflammation.

Published
2021

24. Arginase-II promotes melanoma migration and adhesion through enhancing hydrogen peroxide production and STAT3 signaling

Author

Yu, Yi, Ladeiras, Diogo, Xiong, Yuyan, Boligan, Kayluz Frias, Liang, Xiujie, Gunten, Stephan, Hunger, Robert E., Ming, Xiu‐Fen, and Yang, Zhihong

Subjects
610 Medicine & health
Abstract

Elevated arginase type II (Arg‐II) associates with higher grade tumors. Its function and underlying molecular mechanisms in melanoma remain elusive. In the present study, we observed a significantly higher frequency of Arg‐II expression in melanoma of patients with metastasis than those without metastasis. Silencing Arg‐II in two human melanoma cell lines slowed down the cell growth, while overexpression of native but not a catalytically inactive Arg‐II promoted cell proliferation without affecting cell death. Treatment of cells with arginase inhibitor also reduced melanoma cell number, demonstrating that Arg‐II promotes melanoma cell proliferation dependently of its enzymatic activity. However, results from silencing Arg‐II or overexpressing native or the inactive Arg‐II as well as treatment with arginase inhibitor showed that Arg‐II promotes melanoma metastasis‐related processes, such as melanoma cell migration and adhesion on endothelial cells, independently of its enzymatic activity. Moreover, the treatment of the cells with STAT3 inhibitor suppressed Arg‐II‐promoted melanoma cell migration and adhesion. Furthermore, catalase, but not superoxide dismutase, prevented STAT3 activation as well as increased melanoma cell migration and adhesion induced by overexpressing native or the inactive Arg‐II. Taken together, our study uncovers both activity‐dependent and independent mechanisms of Arg‐II in promoting melanoma progression. While Arg‐II enhances melanoma cell proliferation through polyamine dependently of its enzymatic activity, it promotes metastasis‐ related processes, that is, migration and adhesion onto endothelial cell, through mitochondrial H2O2‐STAT3 pathway independently of the enzymatic activity. Suppressing Arg‐II expression rather than inhibiting its enzymatic activity may, therefore, represent a novel strategy for the treatment of melanoma.

Published
2020
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25. Activation of p70/p85 S6 kinase by a pathway independent of p21ras

Author

Ming, Xiu-Fen, Burgering, Boudewijn M.Th., Wennstrom, Stefan, Claesson-Welsh, Lena, Heldin, Carl-H., Bos, Johannes L., Kozma, Sara C., and Thomas, George

Subjects
Protein kinases -- Research, Enzymes -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A study of the activation of p70 and p85 S6 kinase by a pathway not influenced by p21ras reveals that the activation is stimulated by the sequential activation of the GDP-GTP exchange factor Sos. The p70 and p85 enzymes are two different forms of the same kinase and are essential for mitogenesis. The cells transformed by the activation of this enzyme exhibit increased phosphorylation, which is different from the activities caused by p42 and p44 kinases.

Published
1994

28. Endothelial nitric oxide synthase genetransfer restores endothelium-dependentrelaxations and attenuates lesion formationin carotid arteries in apolipoproteinE-deficient mice

Author

Mujynya-Ludunge, Kathi, Viswambharan, Hema, Driscoll, Robert, Ming, Xiu-Fen, von Segesser, Ludwig, Kappenberger, Lukas, Yang, Zhihong, and Vassalli, Giuseppe

Abstract

Nitric oxide (NO) and monocyte chemoattractant protein-1 (MCP-1) exert partly opposing effects in vascular biology. NO plays pleiotropic vasoprotective roles including vasodilation and inhibition of platelet aggregation, smooth muscle cell proliferation, and endothelial monocyte adhesion, the last effect being mediated by MCP-1 downregulation. Early stages of arteriosclerosis are associated with reduced NO bioactivity and enhanced MCP-1 expression. We have evaluated adenovirus-mediated gene transfer of human endothelial NO synthase (eNOS) and of a N-terminal deletion (8ND) mutant of the MCP-1 gene that acts as a MCP-1 inhibitor in arteriosclerosis-prone, apolipoprotein E-deficient (ApoE-/-) mice. Endotheliumdependent relaxations were impaired in carotid arteries instilled with a noncoding adenoviral vector but were restored by eNOS gene transfer (p < 0.01). A perivascular collar was placed around the common carotid artery to accelerate lesion formation. eNOS gene transfer reduced lesion surface areas, intima/media ratios, and macrophage contents in the media at 5-week follow-up (p < 0.05). In contrast, 8ND-MCP-1 gene transfer did not prevent lesion formation. In conclusion, eNOS gene transfer restores endothelium-dependent vasodilation and inhibits lesion formation in ApoE-/- mouse carotids. Further studies are needed to assess whether vasoprotection is maintained at later disease stages and to evaluate the long-term efficacy of eNOS gene therapy for primary arteriosclerosis

Published
2018

30. Inhibition of S6K1 accounts partially for the anti-inflammatory effects of the arginase inhibitor L-norvaline

Author

Ruffieux Jean, Carvas João, Rajapakse Angana, Ming Xiu-Fen, and Yang Zhihong

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Pharmacological inhibition of endothelial arginase-II has been shown to improve endothelial nitric oxide synthase (eNOS) function and reduce atherogenesis in animal models. We investigated whether the endothelial arginase II is involved in inflammatory responses in endothelial cells. Methods Human endothelial cells were isolated from umbilical veins and stimulated with TNFα (10 ng/ml) for 4 hours. Endothelial expression of the inflammatory molecules i.e. vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin were assessed by immunoblotting. Results The induction of the expression of endothelial VCAM-1, ICAM-1 and E-selectin by TNFα was concentration-dependently reduced by incubation of the endothelial cells with the arginase inhibitor L-norvaline. However, inhibition of arginase by another arginase inhibitor S-(2-boronoethyl)-L-cysteine (BEC) had no effects. To confirm the role of arginase-II (the prominent isoform expressed in HUVECs) in the inflammatory responses, adenoviral mediated siRNA silencing of arginase-II knocked down the arginase II protein level, but did not inhibit the up-regulation of the adhesion molecules. Moreover, the inhibitory effect of L-norvaline was not reversed by the NOS inhibitor L-NAME and L-norvaline did not interfere with TNFα-induced activation of NF-κB, JNK, p38mapk, while it inhibited p70s6k (S6K1) activity. Silencing S6K1 prevented up-regulation of E-selectin, but not that of VCAM-1 or ICAM-1 induced by TNFα. Conclusion The arginase inhibitor L-norvaline exhibits anti-inflammatory effects independently of inhibition of arginase in human endothelial cells. The anti-inflammatory properties of L-norvaline are partially attributable to its ability to inhibit S6K1.

Published
2009
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31. Sirolimus increases tissue factor expression but not activity in cultured human vascular smooth muscle cells

Author

Ming Xiu-Fen, Gajanayake Thusitha, Viswambharan Hema, Zhu Shengsi, and Yang Zhihong

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Sirolimus-eluting stents (CYPHER stents) demonstrated remarkable efficacy in reducing restenosis rates in patients with coronary artery disease. There is a concern of sub-acute and late stent thrombosis. Tissue factor (TF) is critical in thrombosis. This study investigated the effect of sirolimus on TF expression and activity in cultured human vascular smooth muscle cells (SMCs). Methods SMCs were cultured from human saphenous veins and aortas. Quiescent cells were stimulated with sirolimus (0.1 – 20 ng/ml) over 24 hours. Cellular TF expression and activity released into culture medium were measured. The effect of sirolimus on activation of mammalian target of rapamycin (mTOR) was measured by phosphorylation of the substrate p70s6k at T389, and activation of RhoA was measured by pull-down assay. Results Sirolimus increased TF protein level in cultured human SMCs in a concentration and time-dependent manner (about 2-fold, p < 0.01) reaching maximal effect at 5 ng/ml. The stimulation of TF expression by sirolimus was associated with inhibition of basal activity of mTOR. No effects of sirolimus on RhoA or p38mapk activation that are positive regulators of TF in vascular wall cells were observed. The stimulation of TF expression by sirolimus (20 ng/ml) was prevented by the HMG-CoA reductase inhibitor fluvastatin (1 μmol/L). However, no increase in TF activity released from SMC into culture medium was observed after sirolimus treatment. Conclusion Although sirolimus stimulates TF protein expression in human SMC associated with inhibition of mTOR, it does not enhance TF activity released from the cells, suggesting a relatively safe profile of CYPHER stents. The inhibition of TF expression by fluvastatin favors clinical use of statins in patients undergoing coronary stenting.

Published
2005
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32. Arginase-II promotes tumor necrosis Factor-α release from pancreatic acinar cells causing β-cell apoptosis in aging

Author

Xiong, Yuyan, Yepuri, Gautham, Necetin, Sevil, Montani, Jean-Pierre, Ming, Xiu-Fen, and Yang, Zhihong

Abstract

Aging is associated with glucose intolerance. Arginase-II (Arg-II), the type-II L-arginine- ureahydrolase, is highly expressed in pancreas. However, its role in regulation of pancreatic β-cell function is not known. Here we show that female (not male) mice deficient in Arg-II (Arg-II−/−) are protected from age-associated glucose intolerance and reveal greater glucose induced-insulin release, larger islet size and β-cell mass, and more proliferative and less apoptotic β-cells compared with the age-matched wild- type (WT) controls. Moreover, Arg-II is mainly expressed in acinar cells and is upregulated with aging, which enhances p38 mitogen-activated protein kinase (p38 MAPK) activation and release of tumor necrosis factor-α (TNF-α). Accordingly, conditioned medium of isolated acinar cells from old WT (not Arg-II−/−) mice contains higher TNF-α levels than the young mice and stimulates β-cell apoptosis and dysfunction, which are prevented by a neutralizing anti–TNF-α antibody. In acinar cells, our study demonstrates an age-associated Arg-II upregulation, which promotes TNF-α release through p38 MAPK leading to β-cell apoptosis, insufficient insulin secretion, and glucose intolerance in female rather than male mice.

Published
2017

35. Kidney Mass Reduction Leads to l‐Arginine Metabolism‐Dependent Blood Pressure Increase in Mice

Author

Pillai, Samyuktha Muralidharan, Seebeck, Petra, Fingerhut, Ralph, Huang, Ji, Ming, Xiu‐Fen, Yang, Zhihong, Verrey, François; https://orcid.org/0000-0003-3250-9824, Pillai, Samyuktha Muralidharan, Seebeck, Petra, Fingerhut, Ralph, Huang, Ji, Ming, Xiu‐Fen, Yang, Zhihong, and Verrey, François; https://orcid.org/0000-0003-3250-9824

Abstract

BACKGROUND: Uninephrectomy (UNX) is performed for various reasons, including kidney cancer or donation. Kidneys being the main site of l-arginine production in the body, we tested whether UNX mediated kidney mass reduction impacts l-arginine metabolism and thereby nitric oxide production and blood pressure regulation in mice. METHODS AND RESULTS: In a first series of experiments, we observed a significant increase in arterial blood pressure 8 days post-UNX in female and not in male mice. Further experimental series were performed in female mice, and the blood pressure increase was confirmed by telemetry. l-citrulline, that is used in the kidney to produce l-arginine, was elevated post-UNX as was also asymmetric dimethylarginine, an inhibitor of nitric oxide synthase that competes with l-arginine and is a marker for renal failure. Interestingly, the UNX-induced blood pressure increase was prevented by supplementation of the diet with 5% of the l-arginine precursor, l-citrulline. Because l-arginine is metabolized in the kidney and other peripheral tissues by arginase-2, we tested whether the lack of this metabolic pathway also compensates for decreased l-arginine production in the kidney and/or for local nitric oxide synthase inhibition and consecutive blood pressure increase. Indeed, upon uninephrectomy, arginase-2 knockout mice (Arg-2-/-) neither displayed an increase in asymmetric dimethylarginine and l-citrulline plasma levels nor a significant increase in blood pressure. CONCLUSIONS: UNX leads to a small increase in blood pressure that is prevented by l-citrulline supplementation or arginase deficiency, 2 measures that appear to compensate for the impact of kidney mass reduction on l-arginine metabolism

Published
2018

36. Kidney mass reduction leads to L‐arginine metabolism‐dependent blood pressure increase in mice

Author

Muralidharan Pillai, Samyuktha, Seebeck, Petra, Fingerhut, Ralph, Huang, Ji, Ming, Xiu‐Fen, Yang, Zhihong, Verrey, François, Muralidharan Pillai, Samyuktha, Seebeck, Petra, Fingerhut, Ralph, Huang, Ji, Ming, Xiu‐Fen, Yang, Zhihong, and Verrey, François

Abstract

Background Uninephrectomy (UNX) is performed for various reasons, including kidney cancer or donation. Kidneys being the main site of L‐arginine production in the body, we tested whether UNX mediated kidney mass reduction impacts L‐arginine metabolism and thereby nitric oxide production and blood pressure regulation in mice. Methods and Results In a first series of experiments, we observed a significant increase in arterial blood pressure 8 days post‐UNX in female and not in male mice. Further experimental series were performed in female mice, and the blood pressure increase was confirmed by telemetry. L‐citrulline, that is used in the kidney to produce L‐arginine, was elevated post‐UNX as was also asymmetric dimethylarginine, an inhibitor of nitric oxide synthase that competes with L‐arginine and is a marker for renal failure. Interestingly, the UNX‐induced blood pressure increase was prevented by supplementation of the diet with 5% of the L‐arginine precursor, L‐citrulline. Because L‐arginine is metabolized in the kidney and other peripheral tissues by arginase‐2, we tested whether the lack of this metabolic pathway also compensates for decreased L‐arginine production in the kidney and/or for local nitric oxide synthase inhibition and consecutive blood pressure increase. Indeed, upon uninephrectomy, arginase‐2 knockout mice (Arg‐2−/−) neither displayed an increase in asymmetric dimethylarginine and L‐citrulline plasma levels nor a significant increase in blood pressure. Conclusions UNX leads to a small increase in blood pressure that is prevented by L‐ citrulline supplementation or arginase deficiency, 2 measures that appear to compensate for the impact of kidney mass reduction on L‐arginine metabolism.

Published
2018

37. En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries

Author

Yu, Yi, Xiong, Yuyan, Montani, Jean-Pierre, Yang, Zhihong, and Ming, Xiu-Fen

Subjects
Male, Nitric Oxide Synthase Type III, Endothelial Cells, Diet, High-Fat, Nitric Oxide, Mice, Inbred C57BL, Disease Models, Animal, Superoxides, Ethidium, Animals, Fluorescein, Indicators and Reagents, Endothelium, Vascular, Obesity, Molecular Biology, Aorta
Abstract

Endothelium-derived nitric oxide (NO) produced from endothelial NO-synthase (eNOS) is one of the most important vasoprotective molecules in cardiovascular physiology. Dysfunctional eNOS such as uncoupling of eNOS leads to decrease in NO bioavailability and increase in superoxide anion (O₂.−) production, and in turn promotes cardiovascular diseases. Therefore, appropriate measurement of NO and O₂.− levels in the endothelial cells are pivotal for research on cardiovascular diseases and complications. Because of the extremely labile nature of NO and O₂.−, it is difficult to measure NO and O₂.− directly in a blood vessel. Numerous methods have been developed to measure NO and O₂.− production. It is, however, either insensitive, or non-specific, or technically demanding and requires special equipment. Here we describe an adaption of the fluorescence dye method for en face simultaneous detection and visualization of intracellular NO and O₂.− using the cell permeable diaminofluorescein-2 diacetate (DAF-2DA) and dihydroethidium (DHE), respectively, in intact aortas of an obesity mouse model induced by high-fat-diet feeding. We could demonstrate decreased intracellular NO and enhanced O₂.− levels in the freshly isolated intact aortas of obesity mouse as compared to the control lean mouse. We demonstrate that this method is an easy technique for direct detection and visualization of NO and O₂.− in the intact blood vessels and can be widely applied for investigation of endothelial (dys)function under (physio)pathological conditions.

Published
2016

41. Genetic targeting of arginase-ii in mouse prevents renal oxidative stress and inflammation in diet-induced obesity

Author

Huang, Ji, Rajapakse, Angana, Xiong, Yuyan, Montani, Jean-Pierre, Verrey, François, Ming, Xiu-Fen, Yang, Zhihong, Huang, Ji, Rajapakse, Angana, Xiong, Yuyan, Montani, Jean-Pierre, Verrey, François, Ming, Xiu-Fen, and Yang, Zhihong

Abstract

Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L- arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase- II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II−/−) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II−/− mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg- II−/− mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II−/− mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

Published
2017

42. Arginase-ii deficiency extends lifespan in mice

Author

Xiong, Yuyan, Yepuri, Gautham, Montani, Jean-Pierre, Ming, Xiu-Fen, Yang, Zhihong, Xiong, Yuyan, Yepuri, Gautham, Montani, Jean-Pierre, Ming, Xiu-Fen, and Yang, Zhihong

Abstract

The mitochondrial arginase type II (Arg-II) has been shown to interact with ribosomal protein S6 kinase 1 (S6K1) and mitochondrial p66Shc and to promote cell senescence, apoptosis and inflammation under pathological conditions. However, the impact of Arg-II on organismal lifespan is not known. In this study, we demonstrate a significant lifespan extension in mice with Arg-II gene deficiency (Arg-II-/-) as compared to wild type (WT) control animals. This effect is more pronounced in the females than in the males. The gender difference is associated with higher Arg-II expression levels in the females than in the males in skin and heart at both young and old age. Ablation of Arg-II gene significantly reduces the aging marker p16INK4a levels in these tissues of old female mice, whereas in the male mice this effect of Arg- II deficiency is weaker. In line with this observation, age-associated increases in S6K1 signaling and p66Shc levels in heart are significantly attenuated in the female Arg-II-/- mice. In the male mice, only p66Shc but not S6K1 signaling is reduced. In summary, our study demonstrates that Arg-II may play an important role in the acceleration of aging in mice. Genetic disruption of Arg-II in mouse extends lifespan predominantly in females, which relates to inhibition of S6K1, p66Shc, and p16INK4a. Thus, Arg-II may represent a promising target to decelerate aging process and extend lifespan as well as to treat age-related diseases.

Published
2017

44. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

Author

Klionsky, Daniel J., Abdelmohsen, Kotb, Abe, Akihisa, Abedin, Md Joynal, Abeliovich, Hagai, Arozena, Abraham Acevedo, Adachi, Hiroaki, Adams, Christopher M., Adams, Peter D., Adeli, Khosrow, Adhihetty, Peter J., Adler, Sharon G., Agam, Galila, Agarwal, Rajesh, Aghi, Manish K., Agnello, Maria, Agostinis, Patrizia, Aguilar, Patricia V., Aguirre-Ghiso, Julio, Airoldi, Edoardo M., Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akporiaye, Emmanuel T., Al-Rubeai, Mohamed, Albaiceta, Guillermo M., Albanese, Chris, Albani, Diego, Albert, Matthew L., Aldudo, Jesus, Alguel, Hana, Alirezaei, Mehrdad, Alloza, Iraide, Almasan, Alexandru, Almonte-Beceril, Maylin, Alnemri, Emad S., Alonso, Covadonga, Altan-Bonnet, Nihal, Altieri, Dario C., Alvarez, Silvia, Alvarez-Erviti, Lydia, Alves, Sandro, Amadoro, Giuseppina, Amano, Atsuo, Amantini, Consuelo, Ambrosio, Santiago, Amelio, Ivano, Amer, Amal O., Amessou, Mohamed, Amon, Angelika, An, Zhenyi, Anania, Frank A., Andersen, Stig U., Andley, Usha P., Andreadi, Catherine K., Andrieu-Abadie, Nathalie, Anel, Alberto, Ann, David K., Anoopkumar-Dukie, Shailendra, Antonioli, Manuela, Aoki, Hiroshi, Apostolova, Nadezda, Aquila, Saveria, Aquilano, Katia, Araki, Koichi, Arama, Eli, Aranda, Agustin, Araya, Jun, Arcaro, Alexandre, Arias, Esperanza, Arimoto, Hirokazu, Ariosa, Aileen R., Armstrong, Jane L., Arnould, Thierry, Arsov, Ivica, Asanuma, Katsuhiko, Askanas, Valerie, Asselin, Eric, Atarashi, Ryuichiro, Atherton, Sally S., Atkin, Julie D., Attardi, Laura D., Auberger, Patrick, Auburger, Georg, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Avantaggiati, Maria Laura, Avrahami, Limor, Awale, Suresh, Azad, Neelam, Bachetti, Tiziana, Backer, Jonathan M., Bae, Dong-Hun, Bae, Jae-Sung, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric H., Baek, Seung-Hoon, Baghdiguian, Stephen, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xue-Yuan, Bailly, Yannick, Balaji, Kithiganahalli Narayanaswamy, Balduini, Walter, Ballabio, Andrea, Balzan, Rena, Banerjee, Rajkumar, Banhegyi, Gabor, Bao, Haijun, Barbeau, Benoit, Barrachina, Maria D., Barreiro, Esther, Bartel, Bonnie, Bartolome, Alberto, Bassham, Diane C., Bassi, Maria Teresa, Bast, Robert C., Jr., Basu, Alakananda, Batista, Maria Teresa, Batoko, Henri, Battino, Maurizio, Bauckman, Kyle, Baumgarner, Bradley L., Bayer, K. Ulrich, Beale, Rupert, Beaulieu, Jean-Francois, Beck, George R., Jr., Becker, Christoph, Beckham, J. David, Bedard, Pierre-Andre, Bednarski, Patrick J., Begley, Thomas J., Behl, Christian, Behrends, Christian, Behrens, Georg M. N., Behrns, Kevin E., Bejarano, Eloy, Belaid, Amine, Belleudi, Francesca, Benard, Giovanni, Berchem, Guy, Bergamaschi, Daniele, Bergami, Matteo, Berkhout, Ben, Berliocchi, Laura, Bernard, Amelie, Bernard, Monique, Bernassola, Francesca, Bertolotti, Anne, Bess, Amanda S., Besteiro, Sebastien, Bettuzzi, Saverio, Bhalla, Savita, Bhattacharyya, Shalmoli, Bhutia, Sujit K., Biagosch, Caroline, Bianchi, Michele Wolfe, Biard-Piechaczyk, Martine, Billes, Viktor, Bincoletto, Claudia, Bingol, Baris, Bird, Sara W., Bitoun, Marc, Bjedov, Ivana, Blackstone, Craig, Blanc, Lionel, Blanco, Guillermo A., Blomhoff, Heidi Kiil, Boada-Romero, Emilio, Boeckler, Stefan, Boes, Marianne, Boesze-Battaglia, Kathleen, Boise, Lawrence H., Bolino, Alessandra, Boman, Andrea, Bonaldo, Paolo, Bordi, Matteo, Bosch, Jurgen, Botana, Luis M., Botti, Joelle, Bou, German, Bouche, Marina, Bouchecareilh, Marion, Boucher, Marie-Josee, Boulton, Michael E., Bouret, Sebastien G., Boya, Patricia, Boyer-Guittaut, Michaeel, Bozhkov, Peter V., Brady, Nathan, Braga, Vania M. M., Brancolini, Claudio, Braus, Gerhard H., Bravo-San Pedro, Jose M., Brennan, Lisa A., Bresnick, Emery H., Brest, Patrick, Bridges, Dave, Bringer, Marie-Agnes, Brini, Marisa, Brito, Glauber C., Brodin, Bertha, Brookes, Paul S., Brown, Eric J., Brown, Karen, Broxmeyer, Hal E., Bruhat, Alain, Brum, Patricia Chakur, Brumell, John H., Brunetti-Pierri, Nicola, Bryson-Richardson, Robert J., Buch, Shilpa, Buchan, Alastair M., Budak, Hikmet, Bulavin, Dmitry V., Bultman, Scott J., Bultynck, Geert, Bumbasirevic, Vladimir, Burelle, Yan, Burke, Robert E., Burmeister, Margit, Buetikofer, Peter, Caberlotto, Laura, Cadwell, Ken, Cahova, Monika, Cai, Dongsheng, Cai, Jingjing, Cai, Qian, Calatayud, Sara, Camougrand, Nadine, Campanella, Michelangelo, Campbell, Grant R., Campbell, Matthew, Campello, Silvia, Candau, Robin, Caniggia, Isabella, Cantoni, Lavinia, Cao, Lizhi, Caplan, Allan B., Caraglia, Michele, Cardinali, Claudio, Cardoso, Sandra Morais, Carew, Jennifer S., Carleton, Laura A., Carlin, Cathleen R., Carloni, Silvia, Carlsson, Sven R., Carmona-Gutierrez, Didac, Carneiro, Leticia A. M., Carnevali, Oliana, Carra, Serena, Carrier, Alice, Carroll, Bernadette, Casas, Caty, Casas, Josefina, Cassinelli, Giuliana, Castets, Perrine, Castro-Obregon, Susana, Cavallini, Gabriella, Ceccherini, Isabella, Cecconi, Francesco, Cederbaum, Arthur I., Cena, Valentin, Cenci, Simone, Cerella, Claudia, Cervia, Davide, Cetrullo, Silvia, Chaachouay, Hassan, Chae, Han-Jung, Chagin, Andrei S., Chai, Chee-Yin, Chakrabarti, Gopal, Chamilos, Georgios, Chan, Edmond Y. W., Chan, Matthew T. V., Chandra, Dhyan, Chandra, Pallavi, Chang, Chih-Peng, Chang, Raymond Chuen-Chung, Chang, Ta Yuan, Chatham, John C., Chatterjee, Saurabh, Chauhan, Santosh, Che, Yongsheng, Cheetham, Michael E., Cheluvappa, Rajkumar, Chen, Chun-Jung, Chen, Gang, Chen, Guang-Chao, Chen, Guoqiang, Chen, Hongzhuan, Chen, Jeff W., Chen, Jian-Kang, Chen, Min, Chen, Mingzhou, Chen, Peiwen, Chen, Qi, Chen, Quan, Chen, Shang-Der, Chen, Si, Chen, Steve S-L, Chen, Wei, Chen, Wei-Jung, Chen, Wen Qiang, Chen, Wenli, Chen, Xiangmei, Chen, Yau-Hung, Chen, Ye-Guang, Chen, Yin, Chen, Yingyu, Chen, Yongshun, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Yujie, Chen, Zhen, Chen, Zhong, Cheng, Alan, Cheng, Christopher H. K., Cheng, Hua, Cheong, Heesun, Cherry, Sara, Chesney, Jason, Cheung, Chun Hei Antonio, Chevet, Eric, Chi, Hsiang Cheng, Chi, Sung-Gil, Chiacchiera, Fulvio, Chiang, Hui-Ling, Chiarelli, Roberto, Chiariello, Mario, Chieppa, Marcello, Chin, Lih-Shen, Chiong, Mario, Chiu, Gigi N. C., Cho, Dong-Hyung, Cho, Ssang-Goo, Cho, William C., Cho, Yong-Yeon, Cho, Young-Seok, Choi, Augustine M. K., Choi, Eui-Ju, Choi, Eun-Kyoung, Choi, Jayoung, Choi, Mary E., Choi, Seung-Il, Chou, Tsui-Fen, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chow, Kuan-Chih, Chowdhury, Kamal, Chu, Charleen T., Chuang, Tsung-Hsien, Chun, Taehoon, Chung, Hyewon, Chung, Taijoon, Chung, Yuen-Li, Chwae, Yong-Joon, Cianfanelli, Valentina, Ciarcia, Roberto, Ciechomska, Iwona A., Ciriolo, Maria Rosa, Cirone, Mara, Claerhout, Sofie, Clague, Michael J., Claria, Joan, Clarke, Peter G. H., Clarke, Robert, Clementi, Emilio, Cleyrat, Cedric, Cnop, Miriam, Coccia, Eliana M., Cocco, Tiziana, Codogno, Patrice, Coers, Joern, Cohen, Ezra E. W., Colecchia, David, Coletto, Luisa, Coll, Nuria S., Colucci-Guyon, Emma, Comincini, Sergio, Condello, Maria, Cook, Katherine L., Coombs, Graham H., Cooper, Cynthia D., Cooper, J. Mark, Coppens, Isabelle, Corasaniti, Maria Tiziana, Corazzari, Marco, Corbalan, Ramon, Corcelle-Termeau, Elisabeth, Cordero, Mario D., Corral-Ramos, Cristina, Corti, Olga, Cossarizza, Andrea, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Cottet, Sandra, Couve, Eduardo, Covey, Lori R., Cowart, L. Ashley, Cox, Jeffery S., Coxon, Fraser P., Coyne, Carolyn B., Cragg, Mark S., Craven, Rolf J., Crepaldi, Tiziana, Crespo, Jose L., Criollo, Alfredo, Crippa, Valeria, Cruz, Maria Teresa, Cuervo, Ana Maria, Cuezva, Jose M., Cui, Taixing, Cutillas, Pedro R., Czaja, Mark J., Czyzyk-Krzeska, Maria F., Dagda, Ruben K., Dahmen, Uta, Dai, Chunsun, Dai, Wenjie, Dai, Yun, Dalby, Kevin N., Valle, Luisa Dalla, Dalmasso, Guillaume, D'Amelio, Marcello, Damme, Markus, Darfeuille-Michaud, Arlette, Dargemont, Catherine, Darley-Usmar, Victor M., Dasarathy, Srinivasan, Dasgupta, Biplab, Dash, Srikanta, Dass, Crispin R., Davey, Hazel Marie, Davids, Lester M., Davila, David, Davis, Roger J., Dawson, Ted M., Dawson, Valina L., Daza, Paula, de Belleroche, Jackie, de Figueiredo, Paul, Bressan Queiroz de Figueiredo, Regina Celia, de la Fuente, Jose, De Martino, Luisa, De Matteis, Antonella, De Meyer, Guido R. Y., De Milito, Angelo, De Santi, Mauro, de Souza, Wanderley, De Tata, Vincenzo, De Zio, Daniela, Debnath, Jayanta, Dechant, Reinhard, Decuypere, Jean-Paul, Deegan, Shane, Dehay, Benjamin, Del Bello, Barbara, Del Re, Dominic P., Delage-Mourroux, Regis, Delbridge, Lea M. D., Deldicque, Louise, Delorme-Axford, Elizabeth, Deng, Yizhen, Dengjel, Joern, Denizot, Melanie, Dent, Paul, Der, Channing J., Deretic, Vojo, Derrien, Benoit, Deutsch, Eric, Devarenne, Timothy P., Devenish, Rodney J., Di Bartolomeo, Sabrina, Di Daniele, Nicola, Di Domenico, Fabio, Di Nardo, Alessia, Di Paola, Simone, Di Pietro, Antonio, Di Renzo, Livia, DiAntonio, Aaron, Diaz-Araya, Guillermo, Diaz-Laviada, Ines, Diaz-Meco, Maria T., Diaz-Nido, Javier, Dickey, Chad A., Dickson, Robert C., Diederich, Marc, Digard, Paul, Dikic, Ivan, Dinesh-Kumar, Savithrama P., Ding, Chan, Ding, Wen-Xing, Ding, Zufeng, Dini, Luciana, Distler, Joerg H. W., Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dmytruk, Kostyantyn, Dobson, Renwick C. J., Doetsch, Volker, Dokladny, Karol, Dokudovskaya, Svetlana, Donadelli, Massimo, Dong, X. Charlie, Dong, Xiaonan, Dong, Zheng, Donohue, Terrence M., Jr., Doran, Kelly S., D'Orazi, Gabriella, Dorn, Gerald W., II, Dosenko, Victor, Dridi, Sami, Drucker, Liat, Du, Jie, Du, Li-Lin, Du, Lihuan, du Toit, Andre, Dua, Priyamvada, Duan, Lei, Duann, Pu, Dubey, Vikash Kumar, Duchen, Michael R., Duchosal, Michel A., Duez, Helene, Dugail, Isabelle, Dumit, Veronica I., Duncan, Mara C., Dunlop, Elaine A., Dunn, William A., Jr., Dupont, Nicolas, Dupuis, Luc, Duran, Raul V., Durcan, Thomas M., Duvezin-Caubet, Stephane, Duvvuri, Umamaheswar, Eapen, Vinay, Ebrahimi-Fakhari, Darius, Echard, Arnaud, Eckhart, Leopold, Edelstein, Charles L., Edinger, Aimee L., Eichinger, Ludwig, Eisenberg, Tobias, Eisenberg-Lerner, Avital, Eissa, N. Tony, El-Deiry, Wafik S., El-Khoury, Victoria, Elazar, Zvulun, Eldar-Finkelman, Hagit, Elliott, Chris J. H., Emanuele, Enzo, Emmenegger, Urban, Engedal, Nikolai, Engelbrecht, Anna-Mart, Engelender, Simone, Enserink, Jorrit M., Erdmann, Ralf, Erenpreisa, Jekaterina, Eri, Rajaraman, Eriksen, Jason L., Erman, Andreja, Escalante, Ricardo, Eskelinen, Eeva-Liisa, Espert, Lucile, Esteban-Martinez, Lorena, Evans, Thomas J., Fabri, Mario, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Faergeman, Nils J., Faggioni, Alberto, Fairlie, W. Douglas, Fan, Chunhai, Fan, Daping, Fan, Jie, Fang, Shengyun, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Faure, Mathias, Favier, Francois B., Fearnhead, Howard, Federici, Massimo, Fei, Erkang, Felizardo, Tania C., Feng, Hua, Feng, Yibin, Feng, Yuchen, Ferguson, Thomas A., Fernandez, Alvaro F., Fernandez-Barrena, Maite G., Fernandez-Checa, Jose C., Fernandez-Lopez, Arsenio, Fernandez-Zapico, Martin E., Feron, Olivier, Ferraro, Elisabetta, Ferreira-Halder, Carmen Verissima, Fesus, Laszlo, Feuer, Ralph, Fiesel, Fabienne C., Filippi-Chiela, Eduardo C., Filomeni, Giuseppe, Fimia, Gian Maria, Fingert, John H., Finkbeiner, Steven, Finkel, Toren, Fiorito, Filomena, Fisher, Paul B., Flajolet, Marc, Flamigni, Flavio, Florey, Oliver, Florio, Salvatore, Floto, R. Andres, Folini, Marco, Follo, Carlo, Fon, Edward A., Fornai, Francesco, Fortunato, Franco, Fraldi, Alessandro, Franco, Rodrigo, Francois, Arnaud, Francois, Aurelie, Frankel, Lisa B., Fraser, Iain D. C., Frey, Norbert, Freyssenet, Damien G., Frezza, Christian, Friedman, Scott L., Frigo, Daniel E., Fu, Dongxu, Fuentes, Jose M., Fueyo, Juan, Fujitani, Yoshio, Fujiwara, Yuuki, Fujiya, Mikihiro, Fukuda, Mitsunori, Fulda, Simone, Fusco, Carmela, Gabryel, Bozena, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galadari, Sehamuddin, Galili, Gad, Galindo, Inmaculada, Galindo, Maria F., Galliciotti, Giovanna, Galluzzi, Lorenzo, Galluzzi, Luca, Galy, Vincent, Gammoh, Noor, Gandy, Sam, Ganesan, Anand K., Ganesan, Swamynathan, Ganley, Ian G., Gannage, Monique, Gao, Fen-Biao, Gao, Feng, Gao, Jian-Xin, Garcia Nannig, Lorena, Vescovi, Eleonora Garcia, Garcia-Macia, Marina, Garcia-Ruiz, Carmen, Garg, Abhishek D., Garg, Pramod Kumar, Gargini, Ricardo, Gassen, Nils Christian, Gatica, Damian, Gatti, Evelina, Gavard, Julie, Gavathiotis, Evripidis, Ge, Liang, Ge, Pengfei, Ge, Shengfang, Gean, Po-Wu, Gelmetti, Vania, Genazzani, Armando A., Geng, Jiefei, Genschik, Pascal, Gerner, Lisa, Gestwicki, Jason E., Gewirtz, David A., Ghavami, Saeid, Ghigo, Eric, Ghosh, Debabrata, Giammarioli, Anna Maria, Giampieri, Francesca, Giampietri, Claudia, Giatromanolaki, Alexandra, Gibbings, Derrick J., Gibellini, Lara, Gibson, Spencer B., Ginet, Vanessa, Giordano, Antonio, Giorgini, Flaviano, Giovannetti, Elisa, Girardin, Stephen E., Gispert, Suzana, Giuliano, Sandy, Gladson, Candece L., Glavic, Alvaro, Gleave, Martin, Godefroy, Nelly, Gogal, Robert M., Jr., Gokulan, Kuppan, Goldman, Gustavo H., Goletti, Delia, Goligorsky, Michael S., Gomes, Aldrin V., Gomes, Ligia C., Gomez, Hernando, Gomez-Manzano, Candelaria, Gomez-Sanchez, Ruben, Goncalves, Dawit A. P., Goncu, Ebru, Gong, Qingqiu, Gongora, Celine, Gonzalez, Carlos B., Gonzalez-Alegre, Pedro, Gonzalez-Cabo, Pilar, Ana Gonzalez-Polo, Rosa, Goping, Ing Swie, Gorbea, Carlos, Gorbunov, Nikolai V., Goring, Daphne R., Gorman, Adrienne M., Gorski, Sharon M., Goruppi, Sandro, Goto-Yamada, Shino, Gotor, Cecilia, Gottlieb, Roberta A., Gozes, Illana, Gozuacik, Devrim, Graba, Yacine, Graef, Martin, Granato, Giovanna E., Grant, Gary Dean, Grant, Steven, Gravina, Giovanni Luca, Green, Douglas R., Greenhough, Alexander, Greenwood, Michael T., Grimaldi, Benedetto, Gros, Frederic, Grose, Charles, Groulx, Jean-Francois, Gruber, Florian, Grumati, Paolo, Grune, Tilman, Guan, Jun-Lin, Guan, Kun-Liang, Guerra, Barbara, Guillen, Carlos, Gulshan, Kailash, Gunst, Jan, Guo, Chuanyong, Guo, Lei, Guo, Ming, Guo, Wenjie, Guo, Xu-Guang, Gust, Andrea A., Gustafsson, Asa B., Gutierrez, Elaine, Gutierrez, Maximiliano G., Gwak, Ho-Shin, Haas, Albert, Haber, James E., Hadano, Shinji, Hagedorn, Monica, Hahn, David R., Halayko, Andrew J., Hamacher-Brady, Anne, Hamada, Kozo, Hamai, Ahmed, Hamann, Andrea, Hamasaki, Maho, Hamer, Isabelle, Hamid, Qutayba, Hammond, Ester M., Han, Feng, Han, Weidong, Handa, James T., Hanover, John A., Hansen, Malene, Harada, Masaru, Harhaji-Trajkovic, Ljubica, Harper, J. Wade, Harrath, Abdel Halim, Harris, Adrian L., Harris, James, Hasler, Udo, Hasselblatt, Peter, Hasui, Kazuhisa, Hawley, Robert G., Hawley, Teresa S., He, Congcong, He, Cynthia Y., He, Fengtian, He, Gu, He, Rong-Rong, He, Xian-Hui, He, You-Wen, He, Yu-Ying, Heath, Joan K., Hebert, Marie-Josee, Heinzen, Robert A., Helgason, Gudmundur Vignir, Hensel, Michael, Henske, Elizabeth P., Her, Chengtao, Herman, Paul K., Hernandez, Agustin, Hernandez, Carlos, Hernandez-Tiedra, Sonia, Hetz, Claudio, Hiesinger, P. Robin, Higaki, Katsumi, Hilfiker, Sabine, Hill, Bradford G., Hill, Joseph A., Hill, William D., Hino, Keisuke, Hofius, Daniel, Hofman, Paul, Hoeglinger, Guenter U., Hoehfeld, Joerg, Holz, Marina K., Hong, Yonggeun, Hood, David A., Hoozemans, Jeroen J. M., Hoppe, Thorsten, Hsu, Chin, Hsu, Chin-Yuan, Hsu, Li-Chung, Hu, Dong, Hu, Guochang, Hu, Hong-Ming, Hu, Hongbo, Hu, Ming Chang, Hu, Yu-Chen, Hu, Zhuo-Wei, Hua, Fang, Hua, Ya, Huang, Canhua, Huang, Huey-Lan, Huang, Kuo-How, Huang, Kuo-Yang, Huang, Shile, Huang, Shiqian, Huang, Wei-Pang, Huang, Yi-Ran, Huang, Yong, Huang, Yunfei, Huber, Tobias B., Huebbe, Patricia, Huh, Won-Ki, Hulmi, Juha J., Hur, Gang Min, Hurley, James H., Husak, Zvenyslava, Hussain, Sabah N. A., Hussain, Salik, Hwang, Jung Jin, Hwang, Seungmin, Hwang, Thomas I. S., Ichihara, Atsuhiro, Imai, Yuzuru, Imbriano, Carol, Inomata, Megumi, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L., Iozzo, Renato V., Ip, Nancy Y., Irazoqui, Javier E., Iribarren, Pablo, Isaka, Yoshitaka, Isakovic, Aleksandra J., Ischiropoulos, Harry, Isenberg, Jeffrey S., Ishaq, Mohammad, Ishida, Hiroyuki, Ishii, Isao, Ishmael, Jane E., Isidoro, Ciro, Isobe, Ken-ichi, Isono, Erika, Issazadeh-Navikas, Shohreh, Itahana, Koji, Itakura, Eisuke, Ivanov, Andrei I., Iyer, Anand Krishnan V., Izquierdo, Jose M., Izumi, Yotaro, Izzo, Valentina, Jaeaettelae, Marja, Jaber, Nadia, Jackson, Daniel John, Jackson, William T., Jacob, Tony George, Jacques, Thomas S., Jagannath, Chinnaswamy, Jain, Ashish, Jana, Nihar Ranjan, Jang, Byoung Kuk, Jani, Alkesh, Janji, Bassam, Jannig, Paulo Roberto, Jansson, Patric J., Jean, Steve, Jendrach, Marina, Jeon, Ju-Hong, Jessen, Niels, Jeung, Eui-Bae, Jia, Kailiang, Jia, Lijun, Jiang, Hong, Jiang, Hongchi, Jiang, Liwen, Jiang, Teng, Jiang, Xiaoyan, Jiang, Xuejun, Jiang, Ying, Jiang, Yongjun, Jimenez, Alberto, Jin, Cheng, Jin, Hongchuan, Jin, Lei, Jin, Meiyan, Jin, Shengkan, Jinwal, Umesh Kumar, Jo, Eun-Kyeong, Johansen, Terje, Johnson, Daniel E., Johnson, Gail V. W., Johnson, James D., Jonasch, Eric, Jones, Chris, Joosten, Leo A. B., Jordan, Joaquin, Joseph, Anna-Maria, Joseph, Bertrand, Joubert, Annie M., Ju, Dianwen, Ju, Jingfang, Juan, Hsueh-Fen, Juenemann, Katrin, Juhasz, Gabor, Jung, Hye Seung, Jung, Jae U., Jung, Yong-Keun, Jungbluth, Heinz, Justice, Matthew J., Jutten, Barry, Kaakoush, Nadeem O., Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kaeffer, Bertrand, Kagedal, Katarina, Kahana, Alon, Kajimura, Shingo, Kakhlon, Or, Kalia, Manjula, Kalvakolanu, Dhan V., Kamada, Yoshiaki, Kambas, Konstantinos, Kaminskyy, Vitaliy O., Kampinga, Harm H., Kandouz, Mustapha, Kang, Chanhee, Kang, Rui, Kang, Tae-Cheon, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G., Kantorow, Marc, Kaparakis-Liaskos, Maria, Kapuy, Orsolya, Karantza, Vassiliki, Karim, Md Razaul, Karmakar, Parimal, Kaser, Arthur, Kaushik, Susmita, Kawula, Thomas, Kaynar, A. Murat, Ke, Po-Yuan, Ke, Zun-Ji, Kehrl, John H., Keller, Kate E., Kemper, Jongsook Kim, Kenworthy, Anne K., Kepp, Oliver, Kern, Andreas, Kesari, Santosh, Kessel, David, Ketteler, Robin, Kettelhut, Isis do Carmo, Khambu, Bilon, Khan, Muzamil Majid, Khandelwal, Vinoth K. M., Khare, Sangeeta, Kiang, Juliann G., Kiger, Amy A., Kihara, Akio, Kim, Arianna L., Kim, Cheol Hyeon, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Eung Kweon, Kim, Hye Young, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, Jin Hyoung, Kim, Kwang Woon, Kim, Michael D., Kim, Moon-Moo, Kim, Peter K., Kim, Seong Who, Kim, Soo-Youl, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C., Kimura, Tomonori, King, Jason S., Kirkegaard, Karla, Kirkin, Vladimir, Kirshenbaum, Lorrie A., Kishi, Shuji, Kitajima, Yasuo, Kitamoto, Katsuhiko, Kitaoka, Yasushi, Kitazato, Kaio, Kley, Rudolf A., Klimecki, Walter T., Klinkenberg, Michael, Klucken, Jochen, Knaevelsrud, Helene, Knecht, Erwin, Knuppertz, Laura, Ko, Jiunn-Liang, Kobayashi, Satoru, Koch, Jan C., Koechlin-Ramonatxo, Christelle, Koenig, Ulrich, Ko, Young Ho, Koehler, Katja, Kohlwein, Sepp D., Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Dexin, Kong, Hee Jeong, Konstantakou, Eumorphia G., Kopp, Benjamin T., Korcsmaros, Tamas, Korhonen, Laura, Korolchuk, Viktor I., Koshkina, Nadya V., Kou, Yanjun, Koukourakis, Michael I., Koumenis, Constantinos, Kovacs, Attila L., Kovacs, Tibor, Kovacs, Werner J., Koya, Daisuke, Kraft, Claudine, Krainc, Dimitri, Kramer, Helmut, Kravic-Stevovic, Tamara, Krek, Wilhelm, Kretz-Remy, Carole, Krick, Roswitha, Krishnamurthy, Malathi, Kriston-Vizi, Janos, Kroemer, Guido, Kruer, Michael C., Kruger, Rejko, Ktistakis, Nicholas T., Kuchitsu, Kazuyuki, Kuhn, Christian, Kumar, Addanki Pratap, Kumar, Anuj, Kumar, Ashok, Kumar, Deepak, Kumar, Dhiraj, Kumar, Rakesh, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kuno, Atsushi, Kuo, Sheng-Han, Kuret, Jeff, Kurz, Tino, Kwok, Terry, Kwon, Taeg Kyu, Kwon, Yong Tae, Kyrmizi, Irene, La Spada, Albert R., Lafont, Frank, Lahm, Tim, Lakkaraju, Aparna, Lam, Truong, Lamark, Trond, Lancel, Steve, Landowski, Terry H., Lane, Darius J. R., Lane, Jon D., Lanzi, Cinzia, Lapaquette, Pierre, Lapierre, Louis R., Laporte, Jocelyn, Laukkarinen, Johanna, Laurie, Gordon W., Lavandero, Sergio, Lavie, Lena, LaVoie, Matthew J., Law, Betty Yuen Kwan, Law, Helen Ka-wai, Law, Kelsey B., Layfield, Robert, Lazo, Pedro A., Le Cam, Laurent, Le Roch, Karine G., Le Stunff, Herve, Leardkamolkarn, Vijittra, Lecuit, Marc, Lee, Byung-Hoon, Lee, Che-Hsin, Lee, Erinna F., Lee, Gyun Min, Lee, He-Jin, Lee, Hsinyu, Lee, Jae Keun, Lee, Jongdae, Lee, Ju-Hyun, Lee, Jun Hee, Lee, Michael, Lee, Myung-Shik, Lee, Patty J., Lee, Sam W., Lee, Seung-Jae, Lee, Shiow-Ju, Lee, Stella Y., Lee, Sug Hyung, Lee, Sung Sik, Lee, Sung-Joon, Lee, Sunhee, Lee, Ying-Ray, Lee, Yong J., Lee, Young H., Leeuwenburgh, Christiaan, Lefort, Sylvain, Legouis, Renaud, Lei, Jinzhi, Lei, Qun-Ying, Leib, David A., Leibowitz, Gil, Lekli, Istvan, Lemaire, Stephane D., Lemasters, John J., Lemberg, Marius K., Lemoine, Antoinette, Leng, Shuilong, Lenz, Guido, Lenzi, Paola, Lerman, Lilach O., Barbato, Daniele Lettieri, Leu, Julia I-Ju, Leung, Hing Y., Levine, Beth, Lewis, Patrick A., Lezoualc'h, Frank, Li, Chi, Li, Faqiang, Li, Feng-Jun, Li, Jun, Li, Ke, Li, Lian, Li, Min, Li, Qiang, Li, Rui, Li, Sheng, Li, Wei, Li, Xiaotao, Li, Yumin, Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liao, Yulin, Liberal, Joana, Liberski, Pawel P., Lie, Pearl, Lieberman, Andrew P., Lim, Hyunjung Jade, Lim, Kah-Leong, Lim, Kyu, Lima, Raquel T., Lin, Chang-Shen, Lin, Chiou-Feng, Lin, Fang, Lin, Fangming, Lin, Fu-Cheng, Lin, Kui, Lin, Kwang-Huei, Lin, Pei-Hui, Lin, Tianwei, Lin, Wan-Wan, Lin, Yee-Shin, Lin, Yong, Linden, Rafael, Lindholm, Dan, Lindqvist, Lisa M., Lingor, Paul, Linkermann, Andreas, Liotta, Lance A., Lipinski, Marta M., Lira, Vitor A., Lisanti, Michael P., Liton, Paloma B., Liu, Bo, Liu, Chong, Liu, Chun-Feng, Liu, Fei, Liu, Hung-Jen, Liu, Jianxun, Liu, Jing-Jing, Liu, Jing-Lan, Liu, Ke, Liu, Leyuan, Liu, Liang, Liu, Quentin, Liu, Rong-Yu, Liu, Shiming, Liu, Shuwen, Liu, Wei, Liu, Xian-De, Liu, Xiangguo, Liu, Xiao-Hong, Liu, Xinfeng, Liu, Xu, Liu, Xueqin, Liu, Yang, Liu, Yule, Liu, Zexian, Liu, Zhe, Liuzzi, Juan P., Lizard, Gerard, Ljujic, Mila, Lodhi, Irfan J., Logue, Susan E., Lokeshwar, Bal L., Long, Yun Chau, Lonial, Sagar, Loos, Benjamin, Lopez-Otin, Carlos, Lopez-Vicario, Cristina, Lorente, Mar, Lorenzi, Philip L., Lorincz, Peter, Los, Marek, Lotze, Michael T., Lovat, Penny E., Lu, Binfeng, Lu, Bo, Lu, Jiahong, Lu, Qing, Lu, She-Min, Lu, Shuyan, Lu, Yingying, Luciano, Federic, Luckhart, Shirley, Lucocq, John Milton, Ludovico, Paula, Lugea, Aurelia, Lukacs, Nicholas W., Lum, Julian J., Lund, Anders H., Luo, Honglin, Luo, Jia, Luo, Shouqing, Luparello, Claudio, Lyons, Timothy, Ma, Jianjie, Ma, Yi, Ma, Yong, Ma, Zhenyi, Machado, Juliano, Machado-Santelli, Glaucia M., Macian, Fernando, MacIntosh, Gustavo C., MacKeigan, Jeffrey P., Macleod, Kay F., MacMicking, John D., MacMillan-Crow, Lee Ann, Madeo, Frank, Madesh, Muniswamy, Madrigal-Matute, Julio, Maeda, Akiko, Maeda, Tatsuya, Maegawa, Gustavo, Maellaro, Emilia, Maes, Hannelore, Magarinos, Marta, Maiese, Kenneth, Maiti, Tapas K., Maiuri, Luigi, Maiuri, Maria Chiara, Maki, Carl G., Malli, Roland, Malorni, Walter, Maloyan, Alina, Mami-Chouaib, Fathia, Man, Na, Mancias, Joseph D., Mandelkow, Eva-Maria, Mandell, Michael A., Manfredi, Angelo A., Manie, Serge N., Manzoni, Claudia, Mao, Kai, Mao, Zixu, Mao, Zong-Wan, Marambaud, Philippe, Marconi, Anna Maria, Marelja, Zvonimir, Marfe, Gabriella, Margeta, Marta, Margittai, Eva, Mari, Muriel, Mariani, Francesca V., Marin, Concepcio, Marinelli, Sara, Marino, Guillermo, Markovic, Ivanka, Marquez, Rebecca, Martelli, Alberto M., Martens, Sascha, Martin, Katie R., Martin, Seamus J., Martin, Shaun, Martin-Acebes, Miguel A., Martin-Sanz, Paloma, Martinand-Mari, Camille, Martinet, Wim, Martinez, Jennifer, Martinez-Lopez, Nuria, Martinez-Outschoorn, Ubaldo, Martinez-Velazquez, Moises, Martinez-Vicente, Marta, Martins, Waleska Kerllen, Mashima, Hirosato, Mastrianni, James A., Matarese, Giuseppe, Matarrese, Paola, Mateo, Roberto, Matoba, Satoaki, Matsumoto, Naomichi, Matsushita, Takehiko, Matsuura, Akira, Matsuzawa, Takeshi, Mattson, Mark P., Matus, Soledad, Maugeri, Norma, Mauvezin, Caroline, Mayer, Andreas, Maysinger, Dusica, Mazzolini, Guillermo D., McBrayer, Mary Kate, McCall, Kimberly, McCormick, Craig, McInerney, Gerald M., McIver, Skye C., McKenna, Sharon, McMahon, John J., McNeish, Iain A., Mechta-Grigoriou, Fatima, Medema, Jan Paul, Medina, Diego L., Megyeri, Klara, Mehrpour, Maryam, Mehta, Jawahar L., Mei, Yide, Meier, Ute-Christiane, Meijer, Alfred J., Melendez, Alicia, Melino, Gerry, Melino, Sonia, Tenorio de Melo, Edesio Jose, Mena, Maria A., Meneghini, Marc D., Menendez, Javier A., Menezes, Regina, Meng, Liesu, Meng, Ling-hua, Meng, Songshu, Menghini, Rossella, Menko, A. Sue, Menna-Barreto, Rubem F. S., Menon, Manoj B., Meraz-Rios, Marco A., Merla, Giuseppe, Merlini, Luciano, Merlot, Angelica M., Meryk, Andreas, Meschini, Stefania, Meyer, Joel N., Mi, Man-Tian, Miao, Chao-Yu, Micale, Lucia, Michaeli, Simon, Michiels, Carine, Migliaccio, Anna Rita, Mihailidou, Anastasia Susie, Mijaljica, Dalibor, Mikoshiba, Katsuhiko, Milan, Enrico, Miller-Fleming, Leonor, Mills, Gordon B., Mills, Ian G., Minakaki, Georgia, Minassian, Berge A., Ming, Xiu-Fen, Minibayeva, Farida, Minina, Elena A., Mintern, Justine D., Minucci, Saverio, Miranda-Vizuete, Antonio, Mitchell, Claire H., Miyamoto, Shigeki, Miyazawa, Keisuke, Mizushima, Noboru, Mnich, Katarzyna, Mograbi, Baharia, Mohseni, Simin, Moita, Luis Ferreira, Molinari, Marco, Molinari, Maurizio, Moller, Andreas Buch, Mollereau, Bertrand, Mollinedo, Faustino, Monick, Martha M., Montagnaro, Serena, Montell, Craig, Moore, Darren J., Moore, Michael N., Mora-Rodriguez, Rodrigo, Moreira, Paula I., Morel, Etienne, Morelli, Maria Beatrice, Moreno, Sandra, Morgan, Michael J., Moris, Arnaud, Moriyasu, Yuji, Morrison, Janna L., Morrison, Lynda A., Morselli, Eugenia, Moscat, Jorge, Moseley, Pope L., Mostowy, Serge, Motori, Elisa, Mottet, Denis, Mottram, Jeremy C., Moussa, Charbel E-H, Mpakou, Vassiliki E., Mukhtar, Hasan, Levy, Jean M. 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O., Noda, Takeshi, Noegel, Angelika A., Nolte, Elsie Magdalena, Norberg, Erik, Norga, Koenraad K., Noureini, Sakineh Kazemi, Notomi, Shoji, Notterpek, Lucia, Nowikovsky, Karin, Nukina, Nobuyuki, Nuernberger, Thorsten, O'Donnell, Valerie B., O'Donovan, Tracey, O'Dwyer, Peter J., Oehme, Ina, Oeste, Clara L., Ogawa, Michinaga, Ogretmen, Besim, Ogura, Yuji, Oh, Young J., Ohmuraya, Masaki, Ohshima, Takayuki, Ojha, Rani, Okamoto, Koji, Okazaki, Toshiro, Oliver, F. Javier, Ollinger, Karin, Olsson, Stefan, Orban, Daniel P., Ordonez, Paulina, Orhon, Idil, Orosz, Laszlo, O'Rourke, Eyleen J., Orozco, Helena, Ortega, Angel L., Ortona, Elena, Osellame, Laura D., Oshima, Junko, Oshima, Shigeru, Osiewacz, Heinz D., Otomo, Takanobu, Otsu, Kinya, Ou, Jing-hsiung James, Outeiro, Tiago F., Ouyang, Dong-yun, Ouyang, Hongjiao, Overholtzer, Michael, Ozbun, Michelle A., Ozdinler, P. 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M., Carnevali, Oliana, Carra, Serena, Carrier, Alice, Carroll, Bernadette, Casas, Caty, Casas, Josefina, Cassinelli, Giuliana, Castets, Perrine, Castro-Obregon, Susana, Cavallini, Gabriella, Ceccherini, Isabella, Cecconi, Francesco, Cederbaum, Arthur I., Cena, Valentin, Cenci, Simone, Cerella, Claudia, Cervia, Davide, Cetrullo, Silvia, Chaachouay, Hassan, Chae, Han-Jung, Chagin, Andrei S., Chai, Chee-Yin, Chakrabarti, Gopal, Chamilos, Georgios, Chan, Edmond Y. W., Chan, Matthew T. V., Chandra, Dhyan, Chandra, Pallavi, Chang, Chih-Peng, Chang, Raymond Chuen-Chung, Chang, Ta Yuan, Chatham, John C., Chatterjee, Saurabh, Chauhan, Santosh, Che, Yongsheng, Cheetham, Michael E., Cheluvappa, Rajkumar, Chen, Chun-Jung, Chen, Gang, Chen, Guang-Chao, Chen, Guoqiang, Chen, Hongzhuan, Chen, Jeff W., Chen, Jian-Kang, Chen, Min, Chen, Mingzhou, Chen, Peiwen, Chen, Qi, Chen, Quan, Chen, Shang-Der, Chen, Si, Chen, Steve S-L, Chen, Wei, Chen, Wei-Jung, Chen, Wen Qiang, Chen, Wenli, Chen, Xiangmei, Chen, Yau-Hung, Chen, Ye-Guang, Chen, Yin, Chen, Yingyu, Chen, Yongshun, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Yujie, Chen, Zhen, Chen, Zhong, Cheng, Alan, Cheng, Christopher H. K., Cheng, Hua, Cheong, Heesun, Cherry, Sara, Chesney, Jason, Cheung, Chun Hei Antonio, Chevet, Eric, Chi, Hsiang Cheng, Chi, Sung-Gil, Chiacchiera, Fulvio, Chiang, Hui-Ling, Chiarelli, Roberto, Chiariello, Mario, Chieppa, Marcello, Chin, Lih-Shen, Chiong, Mario, Chiu, Gigi N. C., Cho, Dong-Hyung, Cho, Ssang-Goo, Cho, William C., Cho, Yong-Yeon, Cho, Young-Seok, Choi, Augustine M. K., Choi, Eui-Ju, Choi, Eun-Kyoung, Choi, Jayoung, Choi, Mary E., Choi, Seung-Il, Chou, Tsui-Fen, Chouaib, Salem, Choubey, Divaker, Choubey, Vinay, Chow, Kuan-Chih, Chowdhury, Kamal, Chu, Charleen T., Chuang, Tsung-Hsien, Chun, Taehoon, Chung, Hyewon, Chung, Taijoon, Chung, Yuen-Li, Chwae, Yong-Joon, Cianfanelli, Valentina, Ciarcia, Roberto, Ciechomska, Iwona A., Ciriolo, Maria Rosa, Cirone, Mara, Claerhout, Sofie, Clague, Michael J., Claria, Joan, Clarke, Peter G. H., Clarke, Robert, Clementi, Emilio, Cleyrat, Cedric, Cnop, Miriam, Coccia, Eliana M., Cocco, Tiziana, Codogno, Patrice, Coers, Joern, Cohen, Ezra E. W., Colecchia, David, Coletto, Luisa, Coll, Nuria S., Colucci-Guyon, Emma, Comincini, Sergio, Condello, Maria, Cook, Katherine L., Coombs, Graham H., Cooper, Cynthia D., Cooper, J. Mark, Coppens, Isabelle, Corasaniti, Maria Tiziana, Corazzari, Marco, Corbalan, Ramon, Corcelle-Termeau, Elisabeth, Cordero, Mario D., Corral-Ramos, Cristina, Corti, Olga, Cossarizza, Andrea, Costelli, Paola, Costes, Safia, Coto-Montes, Ana, Cottet, Sandra, Couve, Eduardo, Covey, Lori R., Cowart, L. Ashley, Cox, Jeffery S., Coxon, Fraser P., Coyne, Carolyn B., Cragg, Mark S., Craven, Rolf J., Crepaldi, Tiziana, Crespo, Jose L., Criollo, Alfredo, Crippa, Valeria, Cruz, Maria Teresa, Cuervo, Ana Maria, Cuezva, Jose M., Cui, Taixing, Cutillas, Pedro R., Czaja, Mark J., Czyzyk-Krzeska, Maria F., Dagda, Ruben K., Dahmen, Uta, Dai, Chunsun, Dai, Wenjie, Dai, Yun, Dalby, Kevin N., Valle, Luisa Dalla, Dalmasso, Guillaume, D'Amelio, Marcello, Damme, Markus, Darfeuille-Michaud, Arlette, Dargemont, Catherine, Darley-Usmar, Victor M., Dasarathy, Srinivasan, Dasgupta, Biplab, Dash, Srikanta, Dass, Crispin R., Davey, Hazel Marie, Davids, Lester M., Davila, David, Davis, Roger J., Dawson, Ted M., Dawson, Valina L., Daza, Paula, de Belleroche, Jackie, de Figueiredo, Paul, Bressan Queiroz de Figueiredo, Regina Celia, de la Fuente, Jose, De Martino, Luisa, De Matteis, Antonella, De Meyer, Guido R. Y., De Milito, Angelo, De Santi, Mauro, de Souza, Wanderley, De Tata, Vincenzo, De Zio, Daniela, Debnath, Jayanta, Dechant, Reinhard, Decuypere, Jean-Paul, Deegan, Shane, Dehay, Benjamin, Del Bello, Barbara, Del Re, Dominic P., Delage-Mourroux, Regis, Delbridge, Lea M. D., Deldicque, Louise, Delorme-Axford, Elizabeth, Deng, Yizhen, Dengjel, Joern, Denizot, Melanie, Dent, Paul, Der, Channing J., Deretic, Vojo, Derrien, Benoit, Deutsch, Eric, Devarenne, Timothy P., Devenish, Rodney J., Di Bartolomeo, Sabrina, Di Daniele, Nicola, Di Domenico, Fabio, Di Nardo, Alessia, Di Paola, Simone, Di Pietro, Antonio, Di Renzo, Livia, DiAntonio, Aaron, Diaz-Araya, Guillermo, Diaz-Laviada, Ines, Diaz-Meco, Maria T., Diaz-Nido, Javier, Dickey, Chad A., Dickson, Robert C., Diederich, Marc, Digard, Paul, Dikic, Ivan, Dinesh-Kumar, Savithrama P., Ding, Chan, Ding, Wen-Xing, Ding, Zufeng, Dini, Luciana, Distler, Joerg H. W., Diwan, Abhinav, Djavaheri-Mergny, Mojgan, Dmytruk, Kostyantyn, Dobson, Renwick C. J., Doetsch, Volker, Dokladny, Karol, Dokudovskaya, Svetlana, Donadelli, Massimo, Dong, X. Charlie, Dong, Xiaonan, Dong, Zheng, Donohue, Terrence M., Jr., Doran, Kelly S., D'Orazi, Gabriella, Dorn, Gerald W., II, Dosenko, Victor, Dridi, Sami, Drucker, Liat, Du, Jie, Du, Li-Lin, Du, Lihuan, du Toit, Andre, Dua, Priyamvada, Duan, Lei, Duann, Pu, Dubey, Vikash Kumar, Duchen, Michael R., Duchosal, Michel A., Duez, Helene, Dugail, Isabelle, Dumit, Veronica I., Duncan, Mara C., Dunlop, Elaine A., Dunn, William A., Jr., Dupont, Nicolas, Dupuis, Luc, Duran, Raul V., Durcan, Thomas M., Duvezin-Caubet, Stephane, Duvvuri, Umamaheswar, Eapen, Vinay, Ebrahimi-Fakhari, Darius, Echard, Arnaud, Eckhart, Leopold, Edelstein, Charles L., Edinger, Aimee L., Eichinger, Ludwig, Eisenberg, Tobias, Eisenberg-Lerner, Avital, Eissa, N. Tony, El-Deiry, Wafik S., El-Khoury, Victoria, Elazar, Zvulun, Eldar-Finkelman, Hagit, Elliott, Chris J. H., Emanuele, Enzo, Emmenegger, Urban, Engedal, Nikolai, Engelbrecht, Anna-Mart, Engelender, Simone, Enserink, Jorrit M., Erdmann, Ralf, Erenpreisa, Jekaterina, Eri, Rajaraman, Eriksen, Jason L., Erman, Andreja, Escalante, Ricardo, Eskelinen, Eeva-Liisa, Espert, Lucile, Esteban-Martinez, Lorena, Evans, Thomas J., Fabri, Mario, Fabrias, Gemma, Fabrizi, Cinzia, Facchiano, Antonio, Faergeman, Nils J., Faggioni, Alberto, Fairlie, W. Douglas, Fan, Chunhai, Fan, Daping, Fan, Jie, Fang, Shengyun, Fanto, Manolis, Fanzani, Alessandro, Farkas, Thomas, Faure, Mathias, Favier, Francois B., Fearnhead, Howard, Federici, Massimo, Fei, Erkang, Felizardo, Tania C., Feng, Hua, Feng, Yibin, Feng, Yuchen, Ferguson, Thomas A., Fernandez, Alvaro F., Fernandez-Barrena, Maite G., Fernandez-Checa, Jose C., Fernandez-Lopez, Arsenio, Fernandez-Zapico, Martin E., Feron, Olivier, Ferraro, Elisabetta, Ferreira-Halder, Carmen Verissima, Fesus, Laszlo, Feuer, Ralph, Fiesel, Fabienne C., Filippi-Chiela, Eduardo C., Filomeni, Giuseppe, Fimia, Gian Maria, Fingert, John H., Finkbeiner, Steven, Finkel, Toren, Fiorito, Filomena, Fisher, Paul B., Flajolet, Marc, Flamigni, Flavio, Florey, Oliver, Florio, Salvatore, Floto, R. Andres, Folini, Marco, Follo, Carlo, Fon, Edward A., Fornai, Francesco, Fortunato, Franco, Fraldi, Alessandro, Franco, Rodrigo, Francois, Arnaud, Francois, Aurelie, Frankel, Lisa B., Fraser, Iain D. C., Frey, Norbert, Freyssenet, Damien G., Frezza, Christian, Friedman, Scott L., Frigo, Daniel E., Fu, Dongxu, Fuentes, Jose M., Fueyo, Juan, Fujitani, Yoshio, Fujiwara, Yuuki, Fujiya, Mikihiro, Fukuda, Mitsunori, Fulda, Simone, Fusco, Carmela, Gabryel, Bozena, Gaestel, Matthias, Gailly, Philippe, Gajewska, Malgorzata, Galadari, Sehamuddin, Galili, Gad, Galindo, Inmaculada, Galindo, Maria F., Galliciotti, Giovanna, Galluzzi, Lorenzo, Galluzzi, Luca, Galy, Vincent, Gammoh, Noor, Gandy, Sam, Ganesan, Anand K., Ganesan, Swamynathan, Ganley, Ian G., Gannage, Monique, Gao, Fen-Biao, Gao, Feng, Gao, Jian-Xin, Garcia Nannig, Lorena, Vescovi, Eleonora Garcia, Garcia-Macia, Marina, Garcia-Ruiz, Carmen, Garg, Abhishek D., Garg, Pramod Kumar, Gargini, Ricardo, Gassen, Nils Christian, Gatica, Damian, Gatti, Evelina, Gavard, Julie, Gavathiotis, Evripidis, Ge, Liang, Ge, Pengfei, Ge, Shengfang, Gean, Po-Wu, Gelmetti, Vania, Genazzani, Armando A., Geng, Jiefei, Genschik, Pascal, Gerner, Lisa, Gestwicki, Jason E., Gewirtz, David A., Ghavami, Saeid, Ghigo, Eric, Ghosh, Debabrata, Giammarioli, Anna Maria, Giampieri, Francesca, Giampietri, Claudia, Giatromanolaki, Alexandra, Gibbings, Derrick J., Gibellini, Lara, Gibson, Spencer B., Ginet, Vanessa, Giordano, Antonio, Giorgini, Flaviano, Giovannetti, Elisa, Girardin, Stephen E., Gispert, Suzana, Giuliano, Sandy, Gladson, Candece L., Glavic, Alvaro, Gleave, Martin, Godefroy, Nelly, Gogal, Robert M., Jr., Gokulan, Kuppan, Goldman, Gustavo H., Goletti, Delia, Goligorsky, Michael S., Gomes, Aldrin V., Gomes, Ligia C., Gomez, Hernando, Gomez-Manzano, Candelaria, Gomez-Sanchez, Ruben, Goncalves, Dawit A. P., Goncu, Ebru, Gong, Qingqiu, Gongora, Celine, Gonzalez, Carlos B., Gonzalez-Alegre, Pedro, Gonzalez-Cabo, Pilar, Ana Gonzalez-Polo, Rosa, Goping, Ing Swie, Gorbea, Carlos, Gorbunov, Nikolai V., Goring, Daphne R., Gorman, Adrienne M., Gorski, Sharon M., Goruppi, Sandro, Goto-Yamada, Shino, Gotor, Cecilia, Gottlieb, Roberta A., Gozes, Illana, Gozuacik, Devrim, Graba, Yacine, Graef, Martin, Granato, Giovanna E., Grant, Gary Dean, Grant, Steven, Gravina, Giovanni Luca, Green, Douglas R., Greenhough, Alexander, Greenwood, Michael T., Grimaldi, Benedetto, Gros, Frederic, Grose, Charles, Groulx, Jean-Francois, Gruber, Florian, Grumati, Paolo, Grune, Tilman, Guan, Jun-Lin, Guan, Kun-Liang, Guerra, Barbara, Guillen, Carlos, Gulshan, Kailash, Gunst, Jan, Guo, Chuanyong, Guo, Lei, Guo, Ming, Guo, Wenjie, Guo, Xu-Guang, Gust, Andrea A., Gustafsson, Asa B., Gutierrez, Elaine, Gutierrez, Maximiliano G., Gwak, Ho-Shin, Haas, Albert, Haber, James E., Hadano, Shinji, Hagedorn, Monica, Hahn, David R., Halayko, Andrew J., Hamacher-Brady, Anne, Hamada, Kozo, Hamai, Ahmed, Hamann, Andrea, Hamasaki, Maho, Hamer, Isabelle, Hamid, Qutayba, Hammond, Ester M., Han, Feng, Han, Weidong, Handa, James T., Hanover, John A., Hansen, Malene, Harada, Masaru, Harhaji-Trajkovic, Ljubica, Harper, J. Wade, Harrath, Abdel Halim, Harris, Adrian L., Harris, James, Hasler, Udo, Hasselblatt, Peter, Hasui, Kazuhisa, Hawley, Robert G., Hawley, Teresa S., He, Congcong, He, Cynthia Y., He, Fengtian, He, Gu, He, Rong-Rong, He, Xian-Hui, He, You-Wen, He, Yu-Ying, Heath, Joan K., Hebert, Marie-Josee, Heinzen, Robert A., Helgason, Gudmundur Vignir, Hensel, Michael, Henske, Elizabeth P., Her, Chengtao, Herman, Paul K., Hernandez, Agustin, Hernandez, Carlos, Hernandez-Tiedra, Sonia, Hetz, Claudio, Hiesinger, P. Robin, Higaki, Katsumi, Hilfiker, Sabine, Hill, Bradford G., Hill, Joseph A., Hill, William D., Hino, Keisuke, Hofius, Daniel, Hofman, Paul, Hoeglinger, Guenter U., Hoehfeld, Joerg, Holz, Marina K., Hong, Yonggeun, Hood, David A., Hoozemans, Jeroen J. M., Hoppe, Thorsten, Hsu, Chin, Hsu, Chin-Yuan, Hsu, Li-Chung, Hu, Dong, Hu, Guochang, Hu, Hong-Ming, Hu, Hongbo, Hu, Ming Chang, Hu, Yu-Chen, Hu, Zhuo-Wei, Hua, Fang, Hua, Ya, Huang, Canhua, Huang, Huey-Lan, Huang, Kuo-How, Huang, Kuo-Yang, Huang, Shile, Huang, Shiqian, Huang, Wei-Pang, Huang, Yi-Ran, Huang, Yong, Huang, Yunfei, Huber, Tobias B., Huebbe, Patricia, Huh, Won-Ki, Hulmi, Juha J., Hur, Gang Min, Hurley, James H., Husak, Zvenyslava, Hussain, Sabah N. A., Hussain, Salik, Hwang, Jung Jin, Hwang, Seungmin, Hwang, Thomas I. S., Ichihara, Atsuhiro, Imai, Yuzuru, Imbriano, Carol, Inomata, Megumi, Into, Takeshi, Iovane, Valentina, Iovanna, Juan L., Iozzo, Renato V., Ip, Nancy Y., Irazoqui, Javier E., Iribarren, Pablo, Isaka, Yoshitaka, Isakovic, Aleksandra J., Ischiropoulos, Harry, Isenberg, Jeffrey S., Ishaq, Mohammad, Ishida, Hiroyuki, Ishii, Isao, Ishmael, Jane E., Isidoro, Ciro, Isobe, Ken-ichi, Isono, Erika, Issazadeh-Navikas, Shohreh, Itahana, Koji, Itakura, Eisuke, Ivanov, Andrei I., Iyer, Anand Krishnan V., Izquierdo, Jose M., Izumi, Yotaro, Izzo, Valentina, Jaeaettelae, Marja, Jaber, Nadia, Jackson, Daniel John, Jackson, William T., Jacob, Tony George, Jacques, Thomas S., Jagannath, Chinnaswamy, Jain, Ashish, Jana, Nihar Ranjan, Jang, Byoung Kuk, Jani, Alkesh, Janji, Bassam, Jannig, Paulo Roberto, Jansson, Patric J., Jean, Steve, Jendrach, Marina, Jeon, Ju-Hong, Jessen, Niels, Jeung, Eui-Bae, Jia, Kailiang, Jia, Lijun, Jiang, Hong, Jiang, Hongchi, Jiang, Liwen, Jiang, Teng, Jiang, Xiaoyan, Jiang, Xuejun, Jiang, Ying, Jiang, Yongjun, Jimenez, Alberto, Jin, Cheng, Jin, Hongchuan, Jin, Lei, Jin, Meiyan, Jin, Shengkan, Jinwal, Umesh Kumar, Jo, Eun-Kyeong, Johansen, Terje, Johnson, Daniel E., Johnson, Gail V. W., Johnson, James D., Jonasch, Eric, Jones, Chris, Joosten, Leo A. B., Jordan, Joaquin, Joseph, Anna-Maria, Joseph, Bertrand, Joubert, Annie M., Ju, Dianwen, Ju, Jingfang, Juan, Hsueh-Fen, Juenemann, Katrin, Juhasz, Gabor, Jung, Hye Seung, Jung, Jae U., Jung, Yong-Keun, Jungbluth, Heinz, Justice, Matthew J., Jutten, Barry, Kaakoush, Nadeem O., Kaarniranta, Kai, Kaasik, Allen, Kabuta, Tomohiro, Kaeffer, Bertrand, Kagedal, Katarina, Kahana, Alon, Kajimura, Shingo, Kakhlon, Or, Kalia, Manjula, Kalvakolanu, Dhan V., Kamada, Yoshiaki, Kambas, Konstantinos, Kaminskyy, Vitaliy O., Kampinga, Harm H., Kandouz, Mustapha, Kang, Chanhee, Kang, Rui, Kang, Tae-Cheon, Kanki, Tomotake, Kanneganti, Thirumala-Devi, Kanno, Haruo, Kanthasamy, Anumantha G., Kantorow, Marc, Kaparakis-Liaskos, Maria, Kapuy, Orsolya, Karantza, Vassiliki, Karim, Md Razaul, Karmakar, Parimal, Kaser, Arthur, Kaushik, Susmita, Kawula, Thomas, Kaynar, A. Murat, Ke, Po-Yuan, Ke, Zun-Ji, Kehrl, John H., Keller, Kate E., Kemper, Jongsook Kim, Kenworthy, Anne K., Kepp, Oliver, Kern, Andreas, Kesari, Santosh, Kessel, David, Ketteler, Robin, Kettelhut, Isis do Carmo, Khambu, Bilon, Khan, Muzamil Majid, Khandelwal, Vinoth K. M., Khare, Sangeeta, Kiang, Juliann G., Kiger, Amy A., Kihara, Akio, Kim, Arianna L., Kim, Cheol Hyeon, Kim, Deok Ryong, Kim, Do-Hyung, Kim, Eung Kweon, Kim, Hye Young, Kim, Hyung-Ryong, Kim, Jae-Sung, Kim, Jeong Hun, Kim, Jin Cheon, Kim, Jin Hyoung, Kim, Kwang Woon, Kim, Michael D., Kim, Moon-Moo, Kim, Peter K., Kim, Seong Who, Kim, Soo-Youl, Kim, Yong-Sun, Kim, Yonghyun, Kimchi, Adi, Kimmelman, Alec C., Kimura, Tomonori, King, Jason S., Kirkegaard, Karla, Kirkin, Vladimir, Kirshenbaum, Lorrie A., Kishi, Shuji, Kitajima, Yasuo, Kitamoto, Katsuhiko, Kitaoka, Yasushi, Kitazato, Kaio, Kley, Rudolf A., Klimecki, Walter T., Klinkenberg, Michael, Klucken, Jochen, Knaevelsrud, Helene, Knecht, Erwin, Knuppertz, Laura, Ko, Jiunn-Liang, Kobayashi, Satoru, Koch, Jan C., Koechlin-Ramonatxo, Christelle, Koenig, Ulrich, Ko, Young Ho, Koehler, Katja, Kohlwein, Sepp D., Koike, Masato, Komatsu, Masaaki, Kominami, Eiki, Kong, Dexin, Kong, Hee Jeong, Konstantakou, Eumorphia G., Kopp, Benjamin T., Korcsmaros, Tamas, Korhonen, Laura, Korolchuk, Viktor I., Koshkina, Nadya V., Kou, Yanjun, Koukourakis, Michael I., Koumenis, Constantinos, Kovacs, Attila L., Kovacs, Tibor, Kovacs, Werner J., Koya, Daisuke, Kraft, Claudine, Krainc, Dimitri, Kramer, Helmut, Kravic-Stevovic, Tamara, Krek, Wilhelm, Kretz-Remy, Carole, Krick, Roswitha, Krishnamurthy, Malathi, Kriston-Vizi, Janos, Kroemer, Guido, Kruer, Michael C., Kruger, Rejko, Ktistakis, Nicholas T., Kuchitsu, Kazuyuki, Kuhn, Christian, Kumar, Addanki Pratap, Kumar, Anuj, Kumar, Ashok, Kumar, Deepak, Kumar, Dhiraj, Kumar, Rakesh, Kumar, Sharad, Kundu, Mondira, Kung, Hsing-Jien, Kuno, Atsushi, Kuo, Sheng-Han, Kuret, Jeff, Kurz, Tino, Kwok, Terry, Kwon, Taeg Kyu, Kwon, Yong Tae, Kyrmizi, Irene, La Spada, Albert R., Lafont, Frank, Lahm, Tim, Lakkaraju, Aparna, Lam, Truong, Lamark, Trond, Lancel, Steve, Landowski, Terry H., Lane, Darius J. R., Lane, Jon D., Lanzi, Cinzia, Lapaquette, Pierre, Lapierre, Louis R., Laporte, Jocelyn, Laukkarinen, Johanna, Laurie, Gordon W., Lavandero, Sergio, Lavie, Lena, LaVoie, Matthew J., Law, Betty Yuen Kwan, Law, Helen Ka-wai, Law, Kelsey B., Layfield, Robert, Lazo, Pedro A., Le Cam, Laurent, Le Roch, Karine G., Le Stunff, Herve, Leardkamolkarn, Vijittra, Lecuit, Marc, Lee, Byung-Hoon, Lee, Che-Hsin, Lee, Erinna F., Lee, Gyun Min, Lee, He-Jin, Lee, Hsinyu, Lee, Jae Keun, Lee, Jongdae, Lee, Ju-Hyun, Lee, Jun Hee, Lee, Michael, Lee, Myung-Shik, Lee, Patty J., Lee, Sam W., Lee, Seung-Jae, Lee, Shiow-Ju, Lee, Stella Y., Lee, Sug Hyung, Lee, Sung Sik, Lee, Sung-Joon, Lee, Sunhee, Lee, Ying-Ray, Lee, Yong J., Lee, Young H., Leeuwenburgh, Christiaan, Lefort, Sylvain, Legouis, Renaud, Lei, Jinzhi, Lei, Qun-Ying, Leib, David A., Leibowitz, Gil, Lekli, Istvan, Lemaire, Stephane D., Lemasters, John J., Lemberg, Marius K., Lemoine, Antoinette, Leng, Shuilong, Lenz, Guido, Lenzi, Paola, Lerman, Lilach O., Barbato, Daniele Lettieri, Leu, Julia I-Ju, Leung, Hing Y., Levine, Beth, Lewis, Patrick A., Lezoualc'h, Frank, Li, Chi, Li, Faqiang, Li, Feng-Jun, Li, Jun, Li, Ke, Li, Lian, Li, Min, Li, Qiang, Li, Rui, Li, Sheng, Li, Wei, Li, Xiaotao, Li, Yumin, Lian, Jiqin, Liang, Chengyu, Liang, Qiangrong, Liao, Yulin, Liberal, Joana, Liberski, Pawel P., Lie, Pearl, Lieberman, Andrew P., Lim, Hyunjung Jade, Lim, Kah-Leong, Lim, Kyu, Lima, Raquel T., Lin, Chang-Shen, Lin, Chiou-Feng, Lin, Fang, Lin, Fangming, Lin, Fu-Cheng, Lin, Kui, Lin, Kwang-Huei, Lin, Pei-Hui, Lin, Tianwei, Lin, Wan-Wan, Lin, Yee-Shin, Lin, Yong, Linden, Rafael, Lindholm, Dan, Lindqvist, Lisa M., Lingor, Paul, Linkermann, Andreas, Liotta, Lance A., Lipinski, Marta M., Lira, Vitor A., Lisanti, Michael P., Liton, Paloma B., Liu, Bo, Liu, Chong, Liu, Chun-Feng, Liu, Fei, Liu, Hung-Jen, Liu, Jianxun, Liu, Jing-Jing, Liu, Jing-Lan, Liu, Ke, Liu, Leyuan, Liu, Liang, Liu, Quentin, Liu, Rong-Yu, Liu, Shiming, Liu, Shuwen, Liu, Wei, Liu, Xian-De, Liu, Xiangguo, Liu, Xiao-Hong, Liu, Xinfeng, Liu, Xu, Liu, Xueqin, Liu, Yang, Liu, Yule, Liu, Zexian, Liu, Zhe, Liuzzi, Juan P., Lizard, Gerard, Ljujic, Mila, Lodhi, Irfan J., Logue, Susan E., Lokeshwar, Bal L., Long, Yun Chau, Lonial, Sagar, Loos, Benjamin, Lopez-Otin, Carlos, Lopez-Vicario, Cristina, Lorente, Mar, Lorenzi, Philip L., Lorincz, Peter, Los, Marek, Lotze, Michael T., Lovat, Penny E., Lu, Binfeng, Lu, Bo, Lu, Jiahong, Lu, Qing, Lu, She-Min, Lu, Shuyan, Lu, Yingying, Luciano, Federic, Luckhart, Shirley, Lucocq, John Milton, Ludovico, Paula, Lugea, Aurelia, Lukacs, Nicholas W., Lum, Julian J., Lund, Anders H., Luo, Honglin, Luo, Jia, Luo, Shouqing, Luparello, Claudio, Lyons, Timothy, Ma, Jianjie, Ma, Yi, Ma, Yong, Ma, Zhenyi, Machado, Juliano, Machado-Santelli, Glaucia M., Macian, Fernando, MacIntosh, Gustavo C., MacKeigan, Jeffrey P., Macleod, Kay F., MacMicking, John D., MacMillan-Crow, Lee Ann, Madeo, Frank, Madesh, Muniswamy, Madrigal-Matute, Julio, Maeda, Akiko, Maeda, Tatsuya, Maegawa, Gustavo, Maellaro, Emilia, Maes, Hannelore, Magarinos, Marta, Maiese, Kenneth, Maiti, Tapas K., Maiuri, Luigi, Maiuri, Maria Chiara, Maki, Carl G., Malli, Roland, Malorni, Walter, Maloyan, Alina, Mami-Chouaib, Fathia, Man, Na, Mancias, Joseph D., Mandelkow, Eva-Maria, Mandell, Michael A., Manfredi, Angelo A., Manie, Serge N., Manzoni, Claudia, Mao, Kai, Mao, Zixu, Mao, Zong-Wan, Marambaud, Philippe, Marconi, Anna Maria, Marelja, Zvonimir, Marfe, Gabriella, Margeta, Marta, Margittai, Eva, Mari, Muriel, Mariani, Francesca V., Marin, Concepcio, Marinelli, Sara, Marino, Guillermo, Markovic, Ivanka, Marquez, Rebecca, Martelli, Alberto M., Martens, Sascha, Martin, Katie R., Martin, Seamus J., Martin, Shaun, Martin-Acebes, Miguel A., Martin-Sanz, Paloma, Martinand-Mari, Camille, Martinet, Wim, Martinez, Jennifer, Martinez-Lopez, Nuria, Martinez-Outschoorn, Ubaldo, Martinez-Velazquez, Moises, Martinez-Vicente, Marta, Martins, Waleska Kerllen, Mashima, Hirosato, Mastrianni, James A., Matarese, Giuseppe, Matarrese, Paola, Mateo, Roberto, Matoba, Satoaki, Matsumoto, Naomichi, Matsushita, Takehiko, Matsuura, Akira, Matsuzawa, Takeshi, Mattson, Mark P., Matus, Soledad, Maugeri, Norma, Mauvezin, Caroline, Mayer, Andreas, Maysinger, Dusica, Mazzolini, Guillermo D., McBrayer, Mary Kate, McCall, Kimberly, McCormick, Craig, McInerney, Gerald M., McIver, Skye C., McKenna, Sharon, McMahon, John J., McNeish, Iain A., Mechta-Grigoriou, Fatima, Medema, Jan Paul, Medina, Diego L., Megyeri, Klara, Mehrpour, Maryam, Mehta, Jawahar L., Mei, Yide, Meier, Ute-Christiane, Meijer, Alfred J., Melendez, Alicia, Melino, Gerry, Melino, Sonia, Tenorio de Melo, Edesio Jose, Mena, Maria A., Meneghini, Marc D., Menendez, Javier A., Menezes, Regina, Meng, Liesu, Meng, Ling-hua, Meng, Songshu, Menghini, Rossella, Menko, A. Sue, Menna-Barreto, Rubem F. S., Menon, Manoj B., Meraz-Rios, Marco A., Merla, Giuseppe, Merlini, Luciano, Merlot, Angelica M., Meryk, Andreas, Meschini, Stefania, Meyer, Joel N., Mi, Man-Tian, Miao, Chao-Yu, Micale, Lucia, Michaeli, Simon, Michiels, Carine, Migliaccio, Anna Rita, Mihailidou, Anastasia Susie, Mijaljica, Dalibor, Mikoshiba, Katsuhiko, Milan, Enrico, Miller-Fleming, Leonor, Mills, Gordon B., Mills, Ian G., Minakaki, Georgia, Minassian, Berge A., Ming, Xiu-Fen, Minibayeva, Farida, Minina, Elena A., Mintern, Justine D., Minucci, Saverio, Miranda-Vizuete, Antonio, Mitchell, Claire H., Miyamoto, Shigeki, Miyazawa, Keisuke, Mizushima, Noboru, Mnich, Katarzyna, Mograbi, Baharia, Mohseni, Simin, Moita, Luis Ferreira, Molinari, Marco, Molinari, Maurizio, Moller, Andreas Buch, Mollereau, Bertrand, Mollinedo, Faustino, Monick, Martha M., Montagnaro, Serena, Montell, Craig, Moore, Darren J., Moore, Michael N., Mora-Rodriguez, Rodrigo, Moreira, Paula I., Morel, Etienne, Morelli, Maria Beatrice, Moreno, Sandra, Morgan, Michael J., Moris, Arnaud, Moriyasu, Yuji, Morrison, Janna L., Morrison, Lynda A., Morselli, Eugenia, Moscat, Jorge, Moseley, Pope L., Mostowy, Serge, Motori, Elisa, Mottet, Denis, Mottram, Jeremy C., Moussa, Charbel E-H, Mpakou, Vassiliki E., Mukhtar, Hasan, Levy, Jean M. Mulcahy, Muller, Sylviane, Munoz-Moreno, Raquel, Munoz-Pinedo, Cristina, Muenz, Christian, Murphy, Maureen E., Murray, James T., Murthy, Aditya, Mysorekar, Indira U., Nabi, Ivan R., Nabissi, Massimo, Nader, Gustavo A., Nagahara, Yukitoshi, Nagai, Yoshitaka, Nagata, Kazuhiro, Nagelkerke, Anika, Nagy, Peter, Naidu, Samisubbu R., Nair, Sreejayan, Nakano, Hiroyasu, Nakatogawa, Hitoshi, Nanjundan, Meera, Napolitano, Gennaro, Naqvi, Naweed I., Nardacci, Roberta, Narendra, Derek P., Narita, Masashi, Nascimbeni, Anna Chiara, Natarajan, Ramesh, Navegantes, Luiz C., Nawrocki, Steffan T., Nazarko, Taras Y., Nazarko, Volodymyr Y., Neill, Thomas, Neri, Luca M., Netea, Mihai G., Netea-Maier, Romana T., Neves, Bruno M., Ney, Paul A., Nezis, Ioannis P., Nguyen, Hang T. T., Nicot, Anne-Sophie, Nilsen, Hilde, Nilsson, Per, Nishimura, Mikio, Nishino, Ichizo, Niso-Santano, Mireia, Niu, Hua, Nixon, Ralph A., Njar, Vincent C. O., Noda, Takeshi, Noegel, Angelika A., Nolte, Elsie Magdalena, Norberg, Erik, Norga, Koenraad K., Noureini, Sakineh Kazemi, Notomi, Shoji, Notterpek, Lucia, Nowikovsky, Karin, Nukina, Nobuyuki, Nuernberger, Thorsten, O'Donnell, Valerie B., O'Donovan, Tracey, O'Dwyer, Peter J., Oehme, Ina, Oeste, Clara L., Ogawa, Michinaga, Ogretmen, Besim, Ogura, Yuji, Oh, Young J., Ohmuraya, Masaki, Ohshima, Takayuki, Ojha, Rani, Okamoto, Koji, Okazaki, Toshiro, Oliver, F. Javier, Ollinger, Karin, Olsson, Stefan, Orban, Daniel P., Ordonez, Paulina, Orhon, Idil, Orosz, Laszlo, O'Rourke, Eyleen J., Orozco, Helena, Ortega, Angel L., Ortona, Elena, Osellame, Laura D., Oshima, Junko, Oshima, Shigeru, Osiewacz, Heinz D., Otomo, Takanobu, Otsu, Kinya, Ou, Jing-hsiung James, Outeiro, Tiago F., Ouyang, Dong-yun, Ouyang, Hongjiao, Overholtzer, Michael, Ozbun, Michelle A., Ozdinler, P. Hande, Ozpolat, Bulent, Pacelli, Consiglia, Paganetti, Paolo, Page, Guylene, Pages, Gilles, Pagnini, Ugo, Pajak, Beata, Pak, Stephen C., Pakos-Zebrucka, Karolina, Pakpour, Nazzy, Palkova, Zdena, Palladino, Francesca, Pallauf, Kathrin, Pallet, Nicolas, Palmieri, Marta, Paludan, Soren R., Palumbo, Camilla, Palumbo, Silvia, Pampliega, Olatz, Pan, Hongming, Pan, Wei, Panaretakis, Theocharis, Pandey, Aseem, Pantazopoulou, Areti, Papackova, Zuzana, Papademetrio, Daniela L., Papassideri, Issidora, Papini, Alessio, Parajuli, Nirmala, Pardo, Julian, Parekh, Vrajesh V., Parenti, Giancarlo, Park, Jong-In, Park, Junsoo, Park, Ohkmae K., Parker, Roy, Parlato, Rosanna, Parys, Jan B., Parzych, Katherine R., Pasquet, Jean-Max, Pasquier, Benoit, Pasumarthi, Kishore B. S., Patschan, Daniel, Patterson, Cam, Pattingre, Sophie, Pattison, Scott, Pause, Arnim, Pavenstaedt, Hermann, Pavone, Flaminia, Pedrozo, Zully, Pena, Fernando J., Penalva, Miguel A., Pende, Mario, Peng, Jianxin, Penna, Fabio, Penninger, Josef M., Pensalfini, Anna, Pepe, Salvatore, Pereira, Gustavo J. S., Pereira, Paulo C., Perez-de la Cruz, Veronica, Esther Perez-Perez, Maria, Perez-Rodriguez, Diego, Perez-Sala, Dolores, Perier, Celine, Perl, Andras, Perlmutter, David H., Perrotta, Ida, Pervaiz, Shazib, Pesonen, Maija, Pessin, Jeffrey E., Peters, Godefridus J., Petersen, Morten, Petrache, Irina, Petrof, Basil J., Petrovski, Goran, Phang, James M., Piacentini, Mauro, Pierdominici, Marina, Pierre, Philippe, Pierrefite-Carle, Valerie, Pietrocola, Federico, Pimentel-Muinos, Felipe X., Pinar, Mario, Pineda, Benjamin, Pinkas-Kramarski, Ronit, Pinti, Marcello, Pinton, Paolo, Piperdi, Bilal, Piret, James M., Platanias, Leonidas C., Platta, Harald W., Plowey, Edward D., Poggeler, Stefanie, Poirot, Marc, Polcic, Peter, Poletti, Angelo, Poon, Audrey H., Popelka, Hana, Popova, Blagovesta, Poprawa, Izabela, Poulose, Shibu M., Poulton, Joanna, Powers, Scott K., Powers, Ted, Pozuelo-Rubio, Mercedes, Prak, Krisna, Prange, Reinhild, Prescott, Mark, Priault, Muriel, Prince, Sharon, Proia, Richard L., Proikas-Cezanne, Tassula, Prokisch, Holger, Promponas, Vasilis J., Przyklenk, Karin, Puertollano, Rosa, Pugazhenthi, Subbiah, Puglielli, Luigi, Pujol, Aurora, Puyal, Julien, Pyeon, Dohun, Qi, Xin, Qian, Wen-bin, Qin, Zheng-Hong, Qiu, Yu, Qu, Ziwei, Quadrilatero, Joe, Quinn, Frederick, Raben, Nina, Rabinowich, Hannah, Radogna, Flavia, Ragusa, Michael J., Rahmani, Mohamed, Raina, Komal, Ramanadham, Sasanka, Ramesh, Rajagopal, Rami, Abdelhaq, Randall-Demllo, Sarron, Randow, Felix, Rao, Hai, Rao, V. Ashutosh, Rasmussen, Blake B., Rasse, Tobias M., Ratovitski, Edward A., Rautou, Pierre-Emmanuel, Ray, Swapan K., Razani, Babak, Reed, Bruce H., Reggiori, Fulvio, Rehm, Markus, Reichert, Andreas S., Rein, Theo, Reiner, David J., Reits, Eric, Ren, Jun, Ren, Xingcong, Renna, Maurizio, Reusch, Jane E. B., Revuelta, Jose L., Reyes, Leticia, Rezaie, Alireza R., Richards, Robert I., Richardson, Des R., Richetta, Clemence, Riehle, Michael A., Rihn, Bertrand H., Rikihisa, Yasuko, Riley, Brigit E., Rimbach, Gerald, Rippo, Maria Rita, Ritis, Konstantinos, Rizzi, Federica, Rizzo, Elizete, Roach, Peter J., Robbins, Jeffrey, Roberge, Michel, Roca, Gabriela, Roccheri, Maria Carmela, Rocha, Sonia, Rodrigues, Cecilia M. P., Rodriguez, Clara I., Rodriguez de Cordoba, Santiago, Rodriguez-Muela, Natalia, Roelofs, Jeroen, Rogov, Vladimir V., Rohn, Troy T., Rohrer, Baerbel, Romanelli, Davide, Romani, Luigina, Silvia Romano, Patricia, Roncero, M. Isabel G., Luis Rosa, Jose, Rosello, Alicia, Rosen, Kirill V., Rosenstiel, Philip, Rost-Roszkowska, Magdalena, Roth, Kevin A., Roue, Gael, Rouis, Mustapha, Rouschop, Kasper M., Ruan, Daniel T., Ruano, Diego, Rubinsztein, David C., Rucker, Edmund B., III, Rudich, Assaf, Rudolf, Emil, Rudolf, Ruediger, Ruegg, Markus A., Ruiz-Roldan, Carmen, Ruparelia, Avnika Ashok, Rusmini, Paola, Russ, David W., Russo, Gian Luigi, Russo, Giuseppe, Russo, Rossella, Rusten, Tor Erik, Ryabovol, Victoria, Ryan, Kevin M., Ryter, Stefan W., Sabatini, David M., Sacher, Michael, Sachse, Carsten, Sack, Michael N., Sadoshima, Junichi, Saftig, Paul, Sagi-Eisenberg, Ronit, Sahni, Sumit, Saikumar, Pothana, Saito, Tsunenori, Saitoh, Tatsuya, Sakakura, Koichi, Sakoh-Nakatogawa, Machiko, Sakuraba, Yasuhito, Salazar-Roa, Maria, Salomoni, Paolo, Saluja, Ashok K., Salvaterra, Paul M., Salvioli, Rosa, Samali, Afshin, Sanchez, Anthony M. J., Sanchez-Alcazar, Jose A., Sanchez-Prieto, Ricardo, Sandri, Marco, Sanjuan, Miguel A., Santaguida, Stefano, Santambrogio, Laura, Santoni, Giorgio, dos Santos, Claudia Nunes, and Saran, Shweta

Published
2016

45. Guidelines for the use and interpretation of assays for monitoring autophagy:3rd edition

Author

Klionsky, Daniel J, Abdelmohsen, Kotb, Abe, Akihisa, Abedin, Md Joynal, Abeliovich, Hagai, Acevedo Arozena, Abraham, Adachi, Hiroaki, Adams, Christopher M, Adams, Peter D, Adeli, Khosrow, Adhihetty, Peter J, Adler, Sharon G, Agam, Galila, Agarwal, Rajesh, Aghi, Manish K, Agnello, Maria, Agostinis, Patrizia, Aguilar, Patricia V, Aguirre-Ghiso, Julio, Airoldi, Edoardo M, Ait-Si-Ali, Slimane, Akematsu, Takahiko, Akporiaye, Emmanuel T, Al-Rubeai, Mohamed, Albaiceta, Guillermo M, Albanese, Chris, Albani, Diego, Albert, Matthew L, Aldudo, Jesus, Algül, Hana, Alirezaei, Mehrdad, Alloza, Iraide, Almasan, Alexandru, Almonte-Beceril, Maylin, Alnemri, Emad S, Alonso, Covadonga, Altan-Bonnet, Nihal, Altieri, Dario C, Alvarez, Silvia, Alvarez-Erviti, Lydia, Alves, Sandro, Amadoro, Giuseppina, Amano, Atsuo, Amantini, Consuelo, Ambrosio, Santiago, Amelio, Ivano, Amer, Amal O, Amessou, Mohamed, Amon, Angelika, An, Zhenyi, Anania, Frank A, Andersen, Stig U, Andley, Usha P, Andreadi, Catherine K, Andrieu-Abadie, Nathalie, Anel, Alberto, Ann, David K, Anoopkumar-Dukie, Shailendra, Antonioli, Manuela, Aoki, Hiroshi, Apostolova, Nadezda, Aquila, Saveria, Aquilano, Katia, Araki, Koichi, Arama, Eli, Aranda, Agustin, Araya, Jun, Arcaro, Alexandre, Arias, Esperanza, Arimoto, Hirokazu, Ariosa, Aileen R, Armstrong, Jane L, Arnould, Thierry, Arsov, Ivica, Asanuma, Katsuhiko, Askanas, Valerie, Asselin, Eric, Atarashi, Ryuichiro, Atherton, Sally S, Atkin, Julie D, Attardi, Laura D, Auberger, Patrick, Auburger, Georg, Aurelian, Laure, Autelli, Riccardo, Avagliano, Laura, Avantaggiati, Maria Laura, Avrahami, Limor, Awale, Suresh, Azad, Neelam, Bachetti, Tiziana, Backer, Jonathan M, Bae, Dong-Hun, Bae, Jae-Sung, Bae, Ok-Nam, Bae, Soo Han, Baehrecke, Eric H, Baek, Seung-Hoon, Baghdiguian, Stephen, Bagniewska-Zadworna, Agnieszka, Bai, Hua, Bai, Jie, Bai, Xue-Yuan, Bailly, Yannick, Balaji, Kithiganahalli Narayanaswamy, Balduini, Walter, Ballabio, Andrea, Balzan, Rena, Banerjee, Rajkumar, Bánhegyi, Gábor, Bao, Haijun, Barbeau, Benoit, Barrachina, Maria D, Barreiro, Esther, Bartel, Bonnie, Bartolomé, Alberto, Bassham, Diane C, Bassi, Maria Teresa, Bast, Robert C, Basu, Alakananda, Batista, Maria Teresa, Batoko, Henri, Battino, Maurizio, Bauckman, Kyle, Baumgarner, Bradley L, Bayer, K Ulrich, Beale, Rupert, Beaulieu, Jean-François, Beck, George R, Becker, Christoph, Beckham, J David, Bédard, Pierre-André, Bednarski, Patrick J, Begley, Thomas J, Behl, Christian, Behrends, Christian, Behrens, Georg Mn, Behrns, Kevin E, Bejarano, Eloy, Belaid, Amine, Belleudi, Francesca, Bénard, Giovanni, Berchem, Guy, Bergamaschi, Daniele, Bergami, Matteo, Berkhout, Ben, Berliocchi, Laura, Bernard, Amélie, Bernard, Monique, Bernassola, Francesca, Bertolotti, Anne, Bess, Amanda S, Besteiro, Sébastien, Bettuzzi, Saverio, Bhalla, Savita, Bhattacharyya, Shalmoli, Bhutia, Sujit K, Biagosch, Caroline, Bianchi, Michele Wolfe, Biard-Piechaczyk, Martine, Billes, Viktor, Bincoletto, Claudia, Bingol, Baris, Bird, Sara W, Bitoun, Marc, Bjedov, Ivana, Blackstone, Craig, Blanc, Lionel, Blanco, Guillermo A, Blomhoff, Heidi Kiil, Boada-Romero, Emilio, Böckler, Stefan, Boes, Marianne, Boesze-Battaglia, Kathleen, Boise, Lawrence H, Bolino, Alessandra, Boman, Andrea, Bonaldo, Paolo, Bordi, Matteo, Bosch, Jürgen, Botana, Luis M, Botti, Joelle, Bou, German, Bouché, Marina, Bouchecareilh, Marion, Boucher, Marie-Josée, Boulton, Michael E, Bouret, Sebastien G, Boya, Patricia, Boyer-Guittaut, Michaël, Bozhkov, Peter V, Brady, Nathan, Braga, Vania Mm, Brancolini, Claudio, Braus, Gerhard H, Bravo-San Pedro, José M, Brennan, Lisa A, Bresnick, Emery H, Brest, Patrick, Bridges, Dave, Bringer, Marie-Agnès, Brini, Marisa, Brito, Glauber C, Brodin, Bertha, Brookes, Paul S, Brown, Eric J, Brown, Karen, Broxmeyer, Hal E, Bruhat, Alain, Brum, Patricia Chakur, Brumell, John H, Brunetti-Pierri, Nicola, Bryson-Richardson, Robert J, Buch, Shilpa, Buchan, Alastair M, Budak, Hikmet, Bulavin, Dmitry V, Bultman, Scott J, Bultynck, Geert, Bumbasirevic, Vladimir, Burelle, Yan, Burke, Robert E, Burmeister, Margit, Bütikofer, Peter, Caberlotto, Laura, Cadwell, Ken, Cahova, Monika, Cai, Dongsheng, Cai, Jingjing, Cai, Qian, Calatayud, Sara, Camougrand, Nadine, Campanella, Michelangelo, Campbell, Grant R, Campbell, Matthew, Campello, Silvia, Candau, Robin, Caniggia, Isabella, Cantoni, Lavinia, Cao, Lizhi, Caplan, Allan B, Caraglia, Michele, Cardinali, Claudio, Cardoso, Sandra Morais, Carew, Jennifer S, Carleton, Laura A, Carlin, Cathleen R, Carloni, Silvia, Carlsson, Sven R, Carmona-Gutierrez, Didac, Carneiro, Leticia Am, Carnevali, Oliana, Carra, Serena, Carrier, Alice, Carroll, Bernadette, Casas, Caty, Casas, Josefina, Cassinelli, Giuliana, Castets, Perrine, Castro-Obregon, Susana, Cavallini, Gabriella, Ceccherini, Isabella, Cecconi, Francesco, Cederbaum, Arthur I, Ceña, Valentín, Cenci, Simone, Cerella, Claudia, Cervia, Davide, Cetrullo, Silvia, Chaachouay, Hassan, Chae, Han-Jung, Chagin, Andrei S, Chai, Chee-Yin, Chakrabarti, Gopal, Chamilos, Georgios, Chan, Edmond Yw, Chan, Matthew Tv, Chandra, Dhyan, Chandra, Pallavi, Chang, Chih-Peng, Chang, Raymond Chuen-Chung, Chang, Ta Yuan, Chatham, John C, Chatterjee, Saurabh, Chauhan, Santosh, Che, Yongsheng, Cheetham, Michael E, Cheluvappa, Rajkumar, Chen, Chun-Jung, Chen, Gang, Chen, Guang-Chao, Chen, Guoqiang, Chen, Hongzhuan, Chen, Jeff W, Chen, Jian-Kang, Chen, Min, Chen, Mingzhou, Chen, Peiwen, Chen, Qi, Chen, Quan, Chen, Shang-Der, Chen, Si, Chen, Steve S-L, Chen, Wei-Jung, Chen, Wen Qiang, Chen, Wenli, Chen, Xiangmei, Chen, Yau-Hung, Chen, Ye-Guang, Chen, Yin, Chen, Yingyu, Chen, Yongshun, Chen, Yu-Jen, Chen, Yue-Qin, Chen, Yujie, Chen, Zhen, Chen, Zhong, Cheng, Alan, Cheng, Christopher Hk, Cheng, Hua, Cheong, Heesun, Cherry, Sara, Chesney, Jason, Cheung, Chun Hei Antonio, Chevet, Eric, Chi, Hsiang Cheng, Chi, Sung-Gil, Chiacchiera, Fulvio, Chiang, Hui-Ling, Chiarelli, Roberto, Chiariello, Mario, Chieppa, Marcello, Chin, 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Yamashina, Shunhei, Yamashiro, Shigeko, Yan, Bing, Yan, Bo, Yan, Xianghua, Yan, Zhen, Yanagi, Yasuo, Yang, Dun-Sheng, Yang, Jin-Ming, Yang, Liu, Yang, Minghua, Yang, Pei-Ming, Yang, Peixin, Yang, Qian, Yang, Wannian, Yang, Wei Yuan, Yang, Xuesong, Yang, Yi, Yang, Ying, Yang, Zhifen, Yang, Zhihong, Yao, Meng-Chao, Yao, Pamela J, Yao, Xiaofeng, Yao, Zhenyu, Yao, Zhiyuan, Yasui, Linda S, Ye, Mingxiang, Yedvobnick, Barry, Yeganeh, Behzad, Yeh, Elizabeth S, Yeyati, Patricia L, Yi, Fan, Yi, Long, Yin, Xiao-Ming, Yip, Calvin K, Yoo, Yeong-Min, Yoo, Young Hyun, Yoon, Seung-Yong, Yoshida, Ken-Ichi, Yoshimori, Tamotsu, Young, Ken H, Yu, Huixin, Yu, Jane J, Yu, Jin-Tai, Yu, Jun, Yu, Li, Yu, W Haung, Yu, Xiao-Fang, Yu, Zhengping, Yuan, Junying, Yuan, Zhi-Min, Yue, Beatrice Yjt, Yue, Jianbo, Yue, Zhenyu, Zacks, David N, Zacksenhaus, Eldad, Zaffaroni, Nadia, Zaglia, Tania, Zakeri, Zahra, Zecchini, Vincent, Zeng, Jinsheng, Zeng, Min, Zeng, Qi, Zervos, Antonis S, Zhang, Donna D, Zhang, Fan, Zhang, Guo, Zhang, Guo-Chang, Zhang, Hao, Zhang, Hong, Zhang, Hongbing, Zhang, Jian, Zhang, Jiangwei, Zhang, Jianhua, Zhang, Jing-Pu, Zhang, Li, Zhang, Lin, Zhang, Long, Zhang, Ming-Yong, Zhang, Xiangnan, Zhang, Xu Dong, Zhang, Yan, Zhang, Yang, Zhang, Yanjin, Zhang, Yingmei, Zhang, Yunjiao, Zhao, Mei, Zhao, Wei-Li, Zhao, Xiaonan, Zhao, Yan G, Zhao, Ying, Zhao, Yongchao, Zhao, Yu-Xia, Zhao, Zhendong, Zhao, Zhizhuang J, Zheng, Dexian, Zheng, Xi-Long, Zheng, Xiaoxiang, Zhivotovsky, Boris, Zhong, Qing, Zhou, Guang-Zhou, Zhou, Guofei, Zhou, Huiping, Zhou, Shu-Feng, Zhou, Xu-Jie, Zhu, Hongxin, Zhu, Hua, Zhu, Wei-Guo, Zhu, Wenhua, Zhu, Xiao-Feng, Zhu, Yuhua, Zhuang, Shi-Mei, Zhuang, Xiaohong, Ziparo, Elio, Zois, Christos E, Zoladek, Teresa, Zong, Wei-Xing, Zorzano, Antonio, and Zughaier, Susu M

Published
2016

46. Genetic targeting of arginase-II in mouse prevents renal oxidative stress and inflammation in diet-induced obesity

Author

Huang, Ji, Rajapakse, Angana, Xiong, Yuyan, Montani, Jean-Pierre, Verrey, François, Ming, Xiu-Fen, Yang, Zhihong, Huang, Ji, Rajapakse, Angana, Xiong, Yuyan, Montani, Jean-Pierre, Verrey, François, Ming, Xiu-Fen, and Yang, Zhihong

Abstract

Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II(-/-)) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II(-/-) mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II(-/-) mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II(-/-) mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development.

Published
2016

48. mTOR signalling: the molecular interface connecting metabolic stress, aging and cardiovascular diseases

Author

Yang, Zhihong and Ming, Xiu-Fen

Abstract

The continuing increase in the prevalence of obesity and metabolic disorders such as type-II diabetes and an accelerating aging population globally will remain the major contributors to cardiovascular mortality and morbidity in the 21st century. It is well known that aging is highly associated with metabolic and cardiovascular diseases. Growing evidence also shows that obesity and metabolic diseases accelerate aging process. Studies in experimental animal models demonstrate similarity of metabolic and cardiovascular phenotypes in metabolic diseases and old age, e.g. insulin resistance, oxidative stress, chronic low grade inflammation, cardiac hypertrophy, cardiac fibrosis, and heart failure, as well as vascular dysfunctions. Despite intensive research, the molecular mechanisms linking metabolic stress, aging, and ultimately cardiovascular diseases are still elusive. Although the mammalian target of rapamycin (mTOR) signalling is a well known regulator of metabolism and lifespan in model organisms, its central role in linking metabolic stress, aging and cardiovascular diseases is recently emerging. In this article, we review the evidence supporting the role of mTOR signalling as a molecular interface connecting metabolic stress, aging and cardiovascular diseases. The therapeutic potentials of targeting mTOR signalling to protect against metabolic and age-associated cardiovascular diseases are discussed.

Published
2012

49. Arginase iI promotes macrophage inflammatory responses through mitochondrial reactive oxygen species, contributing to insulin resistance and atherogenesis

Author

Ming, Xiu‐Fen, Rajapakse, Angana G., Yepuri, Gautham, Xiong, Yuyan, Carvas, João M., Ruffieux, Jean, Scerri, Isabelle, Wu, Zongsong, Popp, Katja, Li, Jianhui, Sartori, Claudio, Scherrer, Urs, Kwak, Brenda R., Montani, Jean‐Pierre, and Yang, Zhihong

Abstract

Background Macrophage‐mediated chronic inflammation is mechanistically linked to insulin resistance and atherosclerosis. Although arginase I is considered antiinflammatory, the role of arginase II (Arg‐II) in macrophage function remains elusive. This study characterizes the role of Arg‐II in macrophage inflammatory responses and its impact on obesity‐linked type II diabetes mellitus and atherosclerosis.Methods and Results In human monocytes, silencing Arg‐II decreases the monocytes’ adhesion to endothelial cells and their production of proinflammatory mediators stimulated by oxidized low‐density lipoprotein or lipopolysaccharides, as evaluated by real‐time quantitative reverse transcription‐polymerase chain reaction and enzyme‐linked immunosorbent assay. Macrophages differentiated from bone marrow cells of Arg‐II–deficient (Arg‐II−/−) mice express lower levels of lipopolysaccharide‐induced proinflammatory mediators than do macrophages of wild‐type mice. Importantly, reintroducing Arg‐II cDNA into Arg‐II−/− macrophages restores the inflammatory responses, with concomitant enhancement of mitochondrial reactive oxygen species. Scavenging of reactive oxygen species by N‐acetylcysteine prevents the Arg‐II–mediated inflammatory responses. Moreover, high‐fat diet–induced infiltration of macrophages in various organs and expression of proinflammatory cytokines in adipose tissue are blunted in Arg‐II−/− mice. Accordingly, Arg‐II−/− mice reveal lower fasting blood glucose and improved glucose tolerance and insulin sensitivity. Furthermore, apolipoprotein E (ApoE)–deficient mice with Arg‐II deficiency (ApoE−/−Arg‐II−/−) display reduced lesion size with characteristics of stable plaques, such as decreased macrophage inflammation and necrotic core. In vivo adoptive transfer experiments reveal that fewer donor ApoE−/−Arg‐II−/− than ApoE−/−Arg‐II+/+ monocytes infiltrate into the plaque of ApoE−/−Arg‐II+/+ mice. Conversely, recipient ApoE−/−Arg‐II−/− mice accumulate fewer donor monocytes than do recipient ApoE−/−Arg‐II+/+ animals.Conclusions Arg‐II promotes macrophage proinflammatory responses through mitochondrial reactive oxygen species, contributing to insulin resistance and atherogenesis. Targeting Arg‐II represents a potential therapeutic strategy in type II diabetes mellitus and atherosclerosis

Published
2012

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