113 results on '"Li, Guangbi"'
Search Results
102. Enhanced dedifferentiation and injury in mouse podocytes lacking CD38 gene (691.4)
- Author
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Boini, Krishna, primary, Xia, Min, additional, Abais, Justine, additional, Li, Guangbi, additional, and Li, Pin‐Lan, additional
- Published
- 2014
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103. Inhibition of Hyperhomocysteinemia-Induced Inflammasome Activation and Glomerular Sclerosis by NLRP3 Gene Deletion
- Author
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Xia, Min, primary, Conley, Sabena M., additional, Li, Guangbi, additional, Li, Pin-Lan, additional, and Boini, Krishna M., additional
- Published
- 2014
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104. Autophagy maturation associated withCD38‐mediated regulation of lysosome function in mouse glomerular podocytes
- Author
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Xiong, Jing, primary, Xia, Min, additional, Xu, Ming, additional, Zhang, Yang, additional, Abais, Justine M., additional, Li, Guangbi, additional, Riebling, Christopher R., additional, Ritter, Joseph K., additional, Boini, Krishna M., additional, and Li, Pin‐Lan, additional
- Published
- 2013
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105. Non-mercury catalytic acetylene hydrochlorination over activated carbon-supported Au catalysts promoted by CeO2.
- Author
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Li, Guangbi, Li, Wei, and Zhang, Jinli
- Published
- 2016
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106. Exosome Biogenesis and Lysosome Function Determine Podocyte Exosome Release and Glomerular Inflammatory Response during Hyperhomocysteinemia
- Author
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Huang, Dandan, Li, Guangbi, Bhat, Owais M., Zou, Yao, Li, Ningjun, Ritter, Joseph K., and Li, Pin-Lan
- Abstract
Nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation in podocytes is reportedly associated with enhanced release of exosomes containing NLRP3 inflammasome products from these cells during hyperhomocysteinemia (hHcy). We examined the possible role of increased exosome secretion during podocyte NLRP3 inflammasome activation in the glomerular inflammatory response. We tested whether exosome biogenesis and lysosome function are involved in the regulation of exosome release from podocytes during hHcy in mice and upon stimulation of homocysteine (Hcy) in podocytes. By nanoparticle tracking analysis, treatments of mice with amitriptyline (acid sphingomyelinase inhibitor), GW4869 (exosome biogenesis inhibitor), and rapamycin (lysosome function enhancer) were found to inhibit elevated urinary exosomes during hHcy. By examining NLRP3 inflammasome activation in glomeruli during hHcy, amitriptyline (but not GW4869 and rapamycin) was shown to have an inhibitory effect. However, all treatments attenuated glomerular inflammation and injury during hHcy. In cell studies, we showed that Hcy treatment stimulated exosome release from podocytes, which was prevented by amitriptyline, GW4869, and rapamycin. Structured illumination microscopy revealed that Hcy inhibited lysosome–multivesicular body interactions in podocytes, which was prevented by amitriptyline or rapamycin but not GW4869. It is concluded that activation of exosome biogenesis and dysregulated lysosome function are critically implicated in the enhancement of exosome release from podocytes leading to glomerular inflammation and injury during hHcy.
- Published
- 2021
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107. Regulation of exosome release by lysosomal acid ceramidase in coronary arterial endothelial cells: Role of TRPML1 channel.
- Author
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Li G, Huang D, Li P, Yuan X, Yarotskyy V, and Li PL
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- Mice, Animals, Acid Ceramidase genetics, Acid Ceramidase metabolism, Endothelial Cells metabolism, Sphingosine metabolism, Lysosomes metabolism, Mice, Knockout, Mammals metabolism, Exosomes metabolism, Transient Receptor Potential Channels metabolism
- Abstract
Lysosomal acid ceramidase (AC) has been reported to determine multivesicular body (MVB) fate and exosome secretion in different mammalian cells including coronary arterial endothelial cells (CAECs). However, this AC-mediated regulation of exosome release from CAECs and associated underlying mechanism remain poorly understood. In the present study, we hypothesized that AC controls lysosomal Ca
2+ release through TRPML1 channel to regulate exosome release in murine CAECs. To test this hypothesis, we isolated and cultured CAECs from WT/WT and endothelial cell-specific Asah1 gene (gene encoding AC) knockout mice. Using these CAECs, we first demonstrated a remarkable increase in exosome secretion and significant reduction of lysosome-MVB interaction in CAECs lacking Asah1 gene compared to those cells from WT/WT mice. ML-SA1, a TRPML1 channel agonist, was found to enhance lysosome trafficking and increase lysosome-MVB interaction in WT/WT CAECs, but not in CAECs lacking Asah1 gene. However, sphingosine, an AC-derived sphingolipid, was able to increase lysosome movement and lysosome-MVB interaction in CAECs lacking Asah1 gene, leading to reduced exosome release from these cells. Moreover, Asah1 gene deletion was shown to substantially inhibit lysosomal Ca2+ release through suppression of TRPML1 channel activity in CAECs. Sphingosine as an AC product rescued the function of TRPML1 channel in CAECs lacking Asah1 gene. These results suggest that Asah1 gene defect and associated deficiency of AC activity may inhibit TRPML1 channel activity, thereby reducing MVB degradation by lysosome and increasing exosome release from CAECs. This enhanced exosome release from CAECs may contribute to the development of coronary arterial disease under pathological conditions., (Copyright © 2022 Elsevier Inc. All rights reserved.)- Published
- 2022
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108. Podocyte Sphingolipid Signaling in Nephrotic Syndrome.
- Author
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Li G, Kidd J, Gehr TWB, and Li PL
- Subjects
- Animals, Humans, Metabolic Networks and Pathways, Nephrotic Syndrome metabolism, Podocytes metabolism, Nephrotic Syndrome pathology, Podocytes pathology, Signal Transduction, Sphingolipids metabolism
- Abstract
Podocytes play a vital role in the pathogenesis of nephrotic syndrome (NS), which is clinically characterized by heavy proteinuria, hypoalbuminemia, hyperlipidemia, and peripheral edema. The pathogenesis of NS has evolved through several hypotheses ranging from immune dysregulation theory and increased glomerular permeability theory to the current concept of podocytopathy. Podocytopathy is characterized by dysfunction or depletion of podocytes, which may be caused by unknown permeability factor, genetic disorders, drugs, infections, systemic disorders, and hyperfiltration. Over the last two decades, numerous studies have been done to explore the molecular mechanisms of podocyte injuries or NS and to develop the novel therapeutic strategies targeting podocytopathy for treatment of NS. Recent studies have shown that normal sphingolipid metabolism is essential for structural and functional integrity of podocytes. As a basic component of the plasma membrane, sphingolipids not only support the assembly of signaling molecules and interaction of receptors and effectors, but also mediate various cellular activities, such as apoptosis, proliferation, stress responses, necrosis, inflammation, autophagy, senescence, and differentiation. This review briefly summarizes current evidence demonstrating the regulation of sphingolipid metabolism in podocytes and the canonical or noncanonical roles of podocyte sphingolipid signaling in the pathogenesis of NS and associated therapeutic strategies., Competing Interests: The authors declare no conflict of interest., (© Copyright by the Author(s). Published by Cell Physiol Biochem Press.)
- Published
- 2021
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109. Control of lysosomal TRPML1 channel activity and exosome release by acid ceramidase in mouse podocytes.
- Author
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Li G, Huang D, Hong J, Bhat OM, Yuan X, and Li PL
- Subjects
- Acid Ceramidase antagonists & inhibitors, Animals, Cell Line, Transformed, Exosomes drug effects, Fluorouracil analogs & derivatives, Fluorouracil pharmacology, Lysosomes drug effects, Mice, Mice, Inbred C57BL, Podocytes drug effects, Acid Ceramidase metabolism, Exosomes metabolism, Lysosomes metabolism, Podocytes metabolism, Transient Receptor Potential Channels metabolism
- Abstract
The transient receptor potential mucolipin 1 (TRPML1) channel has been reported to mediate lysosomal Ca
2+ release that is involved in Ca2+ -dependent lysosome trafficking and autophagic flux. However, this regulatory mechanism of lysosomal TRPML1 channel activity in podocytes remains poorly understood. In the present study, we tested whether the TRPML1 channel in podocytes mediates lysosome trafficking, which is essential for multivesicular body (MVB) degradation by lysosomes. We first demonstrated the abundant expression of TRPML1 channel in podocytes. By GCaMP3 Ca2+ imaging, we characterized the lysosomal specificity of TRPML1 channel-mediated Ca2+ release in podocytes. Given the important role of acid ceramidase (AC) in lysosome function and podocyte injury, we tested whether AC regulates this TRPML1 channel-mediated Ca2+ release and consequent lysosome-dependent MVB degradation in podocytes. Pharmacologically, it was found that TRPML1 channel activity was remarkably attenuated by the AC inhibitor carmofur. Sphingosine, as an AC product, was demonstrated to induce TRPML1-mediated Ca2+ release, which was inhibited by a TRPML1 blocker, verapamil. Using a Port-a-Patch planar patch-clamp system, we found that AC-associated sphingolipids, sphingomyelin, ceramide, and sphingosine had different effects on TRPML1 channel activity in podocytes. Functionally, the inhibition of AC or blockade of TRPML1 channels was found to suppress the interaction of lysosomes and MVBs, leading to increased exosome release from podocytes. These results suggest that AC is critical for TRPML1 channel-mediated Ca2+ release, which controls lysosome-MVB interaction and exosome release in podocytes.- Published
- 2019
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110. Stimulation of diuresis and natriuresis by renomedullary infusion of a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase.
- Author
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Ahmad A, Daneva Z, Li G, Dempsey SK, Li N, Poklis JL, Lichtman A, Li PL, and Ritter JK
- Subjects
- Amidohydrolases metabolism, Animals, Arachidonic Acids metabolism, Cyclooxygenase 2 metabolism, Endocannabinoids metabolism, Kidney Medulla drug effects, Kidney Medulla metabolism, Male, Mice, Inbred C57BL, Mice, Knockout, Monoacylglycerol Lipases metabolism, Natriuresis drug effects, Natriuresis physiology, Polyunsaturated Alkamides metabolism, Renal Circulation physiology, Amidohydrolases antagonists & inhibitors, Diuresis drug effects, Enzyme Inhibitors pharmacology, Monoacylglycerol Lipases antagonists & inhibitors
- Abstract
The renal medulla, considered critical for the regulation of salt and water balance and long-term blood pressure control, is enriched in anandamide and two of its major metabolizing enzymes, cyclooxygenase-2 (COX-2) and fatty acid amide hydrolase (FAAH). Infusion of anandamide (15, 30, and 60 nmol·min
-1 ·kg-1 ) into the renal medulla of C57BL/6J mice stimulated diuresis and salt excretion in a COX-2- but not COX-1-dependent manner. To determine whether endogenous endocannabinoids in the renal medulla can elicit similar effects, the effects of intramedullary isopropyl dodecyl fluorophosphate (IDFP), which inhibits the two major endocannabinoid hydrolases, were studied. IDFP treatment increased the urine formation rate and sodium excretion in a COX-2- but not COX-1-dependent manner. Neither anandamide nor IDFP affected the glomerular filtration rate. Neither systemic (0.625 mg·kg-1 ·30 min-1 iv) nor intramedullary (15 nmol·min-1 ·kg-1 ·30 min-1 ) IDFP pretreatment before intramedullary anandamide (15-30 nmol·min-1 ·kg-1 ) strictly blocked effects of anandamide, suggesting that hydrolysis of anandamide was not necessary for its diuretic effect. Intramedullary IDFP had no effect on renal blood flow but stimulated renal medullary blood flow. The effects of IDFP on urine flow rate and medullary blood flow were FAAH-dependent as demonstrated using FAAH knockout mice. Analysis of mouse urinary PGE2 concentrations by HPLC-electrospray ionization tandem mass spectrometry showed that IDFP treatment decreased urinary PGE2 These data are consistent with a role of FAAH and endogenous anandamide acting through a COX-2-dependent metabolite to regulate diuresis and salt excretion in the mouse kidney., (Copyright © 2017 the American Physiological Society.)- Published
- 2017
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111. Protective Action of Anandamide and Its COX-2 Metabolite against l-Homocysteine-Induced NLRP3 Inflammasome Activation and Injury in Podocytes.
- Author
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Li G, Xia M, Abais JM, Boini K, Li PL, and Ritter JK
- Subjects
- Animals, Arachidonic Acids pharmacology, Celecoxib metabolism, Celecoxib pharmacology, Cell Line, Cyclooxygenase 2 Inhibitors metabolism, Cyclooxygenase 2 Inhibitors pharmacology, Endocannabinoids pharmacology, Homocysteine metabolism, Hyperhomocysteinemia metabolism, Hyperhomocysteinemia pathology, Male, Mice, Inbred C57BL, Mice, Knockout, NLR Family, Pyrin Domain-Containing 3 Protein antagonists & inhibitors, NLR Family, Pyrin Domain-Containing 3 Protein genetics, Podocytes metabolism, Podocytes pathology, Polyunsaturated Alkamides pharmacology, Arachidonic Acids metabolism, Cyclooxygenase 2 metabolism, Endocannabinoids metabolism, Homocysteine pharmacology, Inflammasomes metabolism, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Podocytes drug effects, Polyunsaturated Alkamides metabolism
- Abstract
Recent studies have demonstrated that l-homocysteine (Hcys)-induced podocyte injury leading to glomerular damage or sclerosis is attributable to the activation of the nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome. Given the demonstrated anti-inflammatory effects of endocannabinoids, the present study was designed to test whether anandamide (AEA) or its metabolites diminish NLRP3 inflammasome activation and prevent podocyte injury and associated glomerular damage during hyperhomocysteinemia (hHcys). AEA (100 μM) inhibited Hcys-induced NLRP3 inflammasome activation in cultured podocytes, as indicated by elevated caspase-1 activity and interleukin-1β levels, and attenuated podocyte dysfunction, as shown by reduced vascular endothelial growth factor production. These effects of AEA were inhibited by the cyclooxygenase-2 (COX-2) inhibitor celecoxib (CEL). In mice in vivo, AEA treatment attenuated glomerular NLRP3 inflammasome activation induced by hHcys accompanying a folate-free diet, on the basis of inhibition of hHcys-induced colocalization of NLRP3 molecules and increased interleukin-1β levels in glomeruli. Correspondingly, AEA prevented hHcys-induced proteinuria, albuminuria, and glomerular damage observed microscopically. Hcys- and AEA-induced effects were absent in NLRP3-knockout mice. These beneficial effects of AEA against hHcys-induced NLRP3 inflammasome activation and glomerular injury were not observed in mice cotreated with CEL. We further demonstrated that prostaglandin E2-ethanolamide (PGE2-EA), a COX-2 product of AEA, at 10 μM had a similar inhibitory effect to that of 100 μM AEA on Hcys-induced NLRP3 inflammasome formation and activation in cultured podocytes. From these results, we conclude that AEA has anti-inflammatory properties, protecting podocytes from Hcys-induced injury by inhibition of NLRP3 inflammasome activation through its COX-2 metabolite, PGE2-EA., (Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.)
- Published
- 2016
- Full Text
- View/download PDF
112. Anandamide and its metabolites: what are their roles in the kidney?
- Author
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Ritter JK, Li G, Xia M, and Boini K
- Subjects
- Animals, Humans, Signal Transduction, Arachidonic Acids metabolism, Endocannabinoids metabolism, Kidney metabolism, Polyunsaturated Alkamides metabolism
- Abstract
Anandamide (AEA) is the N-acyl ethanolamide of arachidonic acid, an agonist of cannabinoid and non-cannabinoid receptors in the body. The kidneys are enriched in AEA and in enzymes that metabolize AEA, but the roles of AEA and its metabolites in the kidney remain poorly understood. This system likely is involved in the regulation of renal blood flow and hemodynamics and of tubular sodium and fluid reabsorption. It may act as a neuromodulator of the renal sympathetic nervous system. AEA and its cyclooxygenase-2 metabolites, the prostamides, in the renal medulla may represent a unique antihypertensive system involved in the long-term control of blood pressure. AEA and its metabolites are also implicated as modulators of inflammation and mediators of signaling in inflammation. AEA and its metabolites may be influential in chronic kidney disease states associated with inflammation and cardiovascular diseases associated with hyperhomocysteinemia. The current knowledge of the roles of AEA and its derivatives highlights the need for further research to define and potentially exploit the role of this endocannabinoid system in the kidney.
- Published
- 2016
- Full Text
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113. Enhanced epithelial-to-mesenchymal transition associated with lysosome dysfunction in podocytes: role of p62/Sequestosome 1 as a signaling hub.
- Author
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Li G, Li CX, Xia M, Ritter JK, Gehr TW, Boini K, and Li PL
- Subjects
- Actins metabolism, CDC2 Protein Kinase metabolism, Cadherins metabolism, Cell Differentiation, Cell Line, Epithelial-Mesenchymal Transition drug effects, Humans, Macrolides pharmacology, Microscopy, Confocal, Mitosis, NF-E2-Related Factor 2 antagonists & inhibitors, NF-E2-Related Factor 2 genetics, NF-E2-Related Factor 2 metabolism, NF-kappa B genetics, NF-kappa B metabolism, Podocytes cytology, Podocytes metabolism, RNA Interference, RNA, Small Interfering metabolism, Sequestosome-1 Protein, Signal Transduction drug effects, Vacuolar Proton-Translocating ATPases antagonists & inhibitors, Vacuolar Proton-Translocating ATPases genetics, Vacuolar Proton-Translocating ATPases metabolism, Zonula Occludens-1 Protein metabolism, Adaptor Proteins, Signal Transducing metabolism, Lysosomes metabolism
- Abstract
Background: Autophagy is of importance in the regulation of cell differentiation and senescence in podocytes. It is possible that derangement of autophagy under different pathological conditions activates or enhances Epithelial-to-Mesenchymal Transition (EMT) in podocytes, resulting in glomerular sclerosis. To test this hypothesis, the present study produced lysosome dysfunction by inhibition of the vacuolar H(+)-ATPase (V-ATPase) to test whether deficiency of autophagic flux leads to enhancement of EMT in podocytes., Methods and Results: By Western blot and confocal analysis, lysosome inhibition using a V-ATPase inhibitor or its siRNA was found to markedly decreases the epithelial markers (P-cadherin and ZO-1) and increases the mesenchymal markers (FSP-1 and α-SMA). This enhancement was accompanied by deficient autophagic flux, as demonstrated by marked increases in LC3B-II and p62/Sequestosome 1. However, inhibition of autophagosome formation using spaudin-1 significantly attenuated both enhancement of EMT and deficiency of autophagic flux. To explore the mechanisms by which deficient autophagic flux enhances EMT, we tested the role of accumulated p62 as a signal hub in this process. Neither the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear kappa-light-chain-enhancer pathways of p62 contributed to enhanced EMT. However, inhibition of cyclin-dependent kinase 1 (CDK1) activity reduced the phosphorylation of p62 and enhanced EMT in podocytes similar to lysosome dysfunction., Conclusion: The lack of phosphorylated p62 leads to a faster exit from cell mitosis, enhanced EMT associated with lysosome dysfunction may be attributed to accumulation of p62 and associated reduction of p62 phosphorylation., (© 2015 S. Karger AG, Basel.)
- Published
- 2015
- Full Text
- View/download PDF
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