40 results on '"Chung, Hun Taeg"'
Search Results
2. Nitric Oxide in Airway Inflammation
- Author
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Lee, Yong Chul, primary, Kim, So Ri, additional, Jo, Eun-Kyeong, additional, Pae, Hyun-Ock, additional, and Chung, Hun-Taeg, additional
- Published
- 2010
- Full Text
- View/download PDF
3. Interactive Relations between Nitric Oxide (NO) and Carbon Monoxide (CO): Heme Oxygenase-1/CO Pathway Is a Key Modulator in NO-Mediated Antiapoptosis and Anti-inflammation
- Author
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Chung, Hun-Taeg, primary, Choi, Byung-Min, additional, Kwon, Young-Guen, additional, and Kim, Young-Myeong, additional
- Published
- 2008
- Full Text
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4. Detection and Measurement for the Modification and Inactivation of Caspase by Nitrosative Stress In Vitro and In Vivo
- Author
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Na, Hee-Jun, primary, Chung, Hun-Taeg, additional, Ha, Kwon-Soo, additional, Lee, Hansoo, additional, Kwon, Young-Guen, additional, Billiar, Timothy R., additional, and Kim, Young-Myeong, additional
- Published
- 2008
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5. [34] In vitro and in vivo modulation of transforming growth factor β1 gene expression by antisense oligomer
- Author
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Chung, Hun-Taeg, primary, Sohn, Dong-Hwan, additional, Choi, Byung-Min, additional, Yoo, Ji-Chang, additional, Pae, Hyun-Ock, additional, and Jun, Chang-Duk, additional
- Published
- 2000
- Full Text
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6. Breast cancer cell debris diminishes therapeutic efficacy through heme oxygenase-1-mediated inactivation of M1-like tumor-associated macrophages.
- Author
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Kim SH, Saeidi S, Zhong X, Gwak SY, Muna IA, Park SA, Kim SH, Na HK, Joe Y, Chung HT, Kim KE, Han W, and Surh YJ
- Subjects
- Animals, Biomarkers, Tumor, Breast Neoplasms etiology, Breast Neoplasms therapy, Cell Line, Tumor, Disease Models, Animal, Disease Susceptibility, Female, Gene Expression Regulation, Neoplastic, Heme Oxygenase-1 metabolism, Humans, Immunophenotyping, Macrophage Activation genetics, Macrophage Activation immunology, Mice, Models, Biological, Phagocytosis genetics, Phagocytosis immunology, Tumor-Associated Macrophages pathology, Breast Neoplasms metabolism, Breast Neoplasms pathology, Heme Oxygenase-1 genetics, Tumor Microenvironment genetics, Tumor Microenvironment immunology, Tumor-Associated Macrophages immunology, Tumor-Associated Macrophages metabolism
- Abstract
Chemotherapy is commonly used as a major therapeutic option for breast cancer treatment, but its efficacy is often diminished by disruption of patient's anti-tumor immunity. Chemotherapy-generated tumor cell debris could hijack accumulated tumor-associated macrophages (TAMs), provoking tumor recurrence. Therefore, reprogramming TAMs to acquire an immunocompetent phenotype is a promising strategy to potentiate therapeutic efficacy. In this study, we analyzed the proportion of immune cells in the breast cancer patients who received chemotherapy. To validate our findings in vivo, we used a syngeneic murine breast cancer (4T1) model. Chemotherapy generates an immunosuppressive tumor microenvironment in breast cancer. Here, we show that phagocytic engulfment of tumor cell debris by TAMs reduces chemotherapeutic efficacy in a 4T1 breast cancer model. Specifically, the engulfment of tumor cell debris by macrophages reduced M1-like polarization through heme oxygenase-1 (HO-1) upregulation. Conversely, genetic or pharmacologic inhibition of HO-1 in TAMs restored the M1-like polarization. Our results demonstrate that tumor cell debris-induced HO-1 expression in macrophages regulates their polarization. Inhibition of HO-1 overexpression in TAMs may provoke a robust anti-tumor immune response, thereby potentiating the efficacy of chemotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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7. Progress in heme oxygenase research.
- Author
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Surh YJ, Chung HT, Na HK, Dulak J, and Stec DE
- Subjects
- Congresses as Topic, Heme Oxygenase (Decyclizing) metabolism, Heme Oxygenase (Decyclizing) physiology
- Published
- 2020
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8. CO ameliorates endothelial senescence induced by 5-fluorouracil through SIRT1 activation.
- Author
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Zheng M, Chen Y, Park J, Song HC, Chen Y, Park JW, Joe Y, and Chung HT
- Subjects
- Antioxidants pharmacology, Down-Regulation, Heme Oxygenase-1 metabolism, Human Umbilical Vein Endothelial Cells pathology, Humans, Nitric Oxide Synthase Type III metabolism, Reactive Oxygen Species metabolism, Carbon Monoxide pharmacology, Cellular Senescence drug effects, Fluorouracil pharmacology, Human Umbilical Vein Endothelial Cells drug effects, Sirtuin 1 metabolism
- Abstract
Endothelial senescence is the main risk factor that contributes to vascular dysfunction and the progression of vascular disease. Carbon monoxide (CO) plays an important role in preventing vascular dysfunction and in maintaining vascular physiology or homeostasis. The application of exogenous CO has been shown to confer protection in several models of cardiovascular injury or disease, including hypertension, atherosclerosis, balloon-catheter injury, and graft rejection. However, the mechanism by which CO prevents endothelial senescence has been largely unexplored. The aim of this study was to evaluate the effects of CO on endothelial senescence and to investigate the possible mechanisms underlying this process. We measured the levels of senescence-associated-β-galactosidase activity, senescence-associated secretory phenotype, reactive oxygen species (ROS) production, and stress granule in human umbilical vein endothelial cells and the WI-38 human diploid fibroblast cell line. We found that 5-fluorouracil (5FU)-induced ROS generation was inhibited by CO-releasing molecules (CORM)-A1 treatment, and endothelial senescence induced by 5FU was attenuated by CORM-A1 treatment. The SIRT1 inhibitor EX527 reversed the inhibitory effect of CO on the 5FU-induced endothelial senescence. Furthermore, SIRT1 deficiency abolished the stress granule formation by CO. Our results suggest that CO alleviates the endothelial senescence induced by 5FU through SIRT1 activation and may hence have therapeutic potential for the treatment of vascular diseases., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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9. The Essential Role of Ca 2+ Signals in UVB-Induced IL-1β Secretion in Keratinocytes.
- Author
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Park KH, Park DR, Kim YW, Nam TS, Jang KY, Chung HT, and Kim UH
- Subjects
- ADP-ribosyl Cyclase 1 antagonists & inhibitors, ADP-ribosyl Cyclase 1 genetics, ADP-ribosyl Cyclase 1 metabolism, Animals, Antioxidants pharmacology, Calcium metabolism, Calcium Signaling drug effects, Calcium Signaling radiation effects, Carcinogenesis immunology, Carcinogenesis radiation effects, Cations, Divalent metabolism, Cell Line, Epidermis immunology, Epidermis metabolism, Humans, Interleukin-1beta immunology, Membrane Glycoproteins antagonists & inhibitors, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Mice, Mice, Knockout, Models, Animal, NADPH Oxidase 4 antagonists & inhibitors, NADPH Oxidase 4 genetics, NADPH Oxidase 4 metabolism, Photosensitivity Disorders etiology, Photosensitivity Disorders immunology, Primary Cell Culture, Reactive Oxygen Species immunology, Reactive Oxygen Species metabolism, Skin Aging immunology, Skin Aging radiation effects, Calcium Signaling immunology, Epidermis radiation effects, Interleukin-1beta metabolism, Ultraviolet Rays adverse effects
- Abstract
UVB-induced skin damage is attributable to reactive oxygen species, which are triggered by intracellular Ca
2+ signals. However, exactly how the reactive oxygen species are triggered by intracellular Ca2+ upon UVB irradiation remains obscure. Here, we show that UVB induces Ca2+ signals via sequential generation of the following Ca2+ messengers: inositol 1,4,5-trisphosphate, nicotinic acid adenine dinucleotide phosphate, and cyclic ADP-ribose. UVB induced H2 O2 production through NADPH oxidase 4 activation, which is downstream to inositol 1,4,5-trisphosphate and nicotinic acid adenine dinucleotide phosphate. H2 O2 derived from NADPH oxidase 4 activated CD38 to produce cyclic ADP-ribose. UVB first evoked the pannexin channel to release ATP, which acts on P2X7 receptor to generate inositol 1,4,5-trisphosphate. Inhibitors of these messengers, as well as antioxidants, blocked UVB-induced Ca2+ signals and IL-1β secretion in keratinocytes. Furthermore, ablation of CD38 and NADPH oxidase 4 protected against UVB-induced inflammation and IL-1β secretion in the murine epidermis. These results show that UVB induces IL-1β secretion through cross-talk between Ca2+ and reactive oxygen species, providing insight towards potential targets against UVB-induced inflammation., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2019
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10. Carbon monoxide induces the assembly of stress granule through the integrated stress response.
- Author
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Chen Y, Joe Y, Park J, Song HC, Kim UH, and Chung HT
- Subjects
- Animals, Cell Line, Eukaryotic Initiation Factor-2 metabolism, Fibroblasts metabolism, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Mitochondria drug effects, Mitochondria metabolism, Organometallic Compounds pharmacology, Reactive Oxygen Species metabolism, Signal Transduction drug effects, eIF-2 Kinase metabolism, Carbon Monoxide pharmacology, Cytoplasmic Granules drug effects, Cytoplasmic Granules metabolism, Stress, Physiological drug effects
- Abstract
Stress granules (SGs) are membraneless and phase-dense organelles that form transiently in response to a variety of harmful stimuli, including oxidative, heat, osmotic, ultraviolet light and chemotoxic stresses, and thus providing protective effects, allowing survivals. Carbon monoxide (CO), a gaseous second messenger, is synthesized by heme-oxygenases, and exerts anti-inflammatory, anti-proliferative and anti-apoptotic effects in a variety of cellular- and tissue-injury models. Several reports indicate that low levels of mitochondrial reactive oxygen species (mtROS) generated by CO can selectively activate PERK-eIF2α integrated stress response (ISR) to preserve the cellular homeostasis. Hence, CO can confer protection against cellular stresses. However, the mechanisms underlying the cyto-protective effects of CO against various harmful stimuli remain to be elucidated. Here, we sought to examine whether CO induces the SG assembly, and uncover its molecular mechanisms. We treated WI-38 cells and primary mouse embryonic fibroblasts (MEFs) with CO-releasing molecule 2 (CORM2) or CO gas, and found the SG assemblies were gradually increased in time and dose dependent manners. Next, we used Mito-TEMPO, an mtROS scavenger, to explore if mtROS might be involved in the CO-induced SG assembly. Furthermore, we confirmed the involvement of ISR consisted of PERK-eIF2α signaling pathway induced by CO for the SGs assembly. Finally, the inhibition of SG assembly by ISR inhibitor further verified CO-induced ISR might be responsible for SG. Taken together, in this study, we first demonstrated that CO is a novel SG inducer by activating ISR. Moreover, mtROS might be an initiator for the CO-induced ISR responsible for SG assembly., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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11. Role of heme oxygenase-1 in potentiation of phagocytic activity of macrophages by taurine chloramine: Implications for the resolution of zymosan A-induced murine peritonitis.
- Author
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Kim W, Kim SH, Jang JH, Kim C, Kim K, Suh YG, Joe Y, Chung HT, Cha YN, and Surh YJ
- Subjects
- Animals, Antioxidants, Inflammation, Macrophages physiology, Macrophages, Peritoneal, Mice, Mice, Inbred C57BL, Mice, Knockout, Peritonitis chemically induced, Peritonitis physiopathology, Phagocytes, Phagocytosis physiology, RAW 264.7 Cells, Taurine metabolism, Taurine pharmacology, Up-Regulation, Zymosan pharmacology, Heme Oxygenase-1 metabolism, Heme Oxygenase-1 physiology, Taurine analogs & derivatives
- Abstract
Phagocytosis of pathogens by macrophages is crucial for the successful resolution of inflammation induced by microbial infection. Taurine chloramine (TauCl), an endogenous anti-inflammatory and antioxidative substance, is produced by reaction between taurine and hypochlorous acid by myeloperoxidase activity in neutrophils under inflammatory conditions. In the present study, we investigated the effect of TauCl on resolution of acute inflammation caused by fungal infection using a zymosan A-induced murine peritonitis model. TauCl administration reduced the number of the total peritoneal leukocytes, while it increased the number of peritoneal monocytes. Furthermore, TauCl promoted clearance of pathogens remaining in the inflammatory environment by macrophages. When the macrophages isolated from thioglycollate-treated mice were treated with TauCl, their phagocytic capability was enhanced. In the murine macrophage-like RAW264.7 cells treated with TauCl, the proportion of macrophages clearing the zymosan A particles was also increased. TauCl administration resulted in elevated expression of heme oxygenase-1 (HO-1) in the peritoneal macrophages. Pharmacologic inhibition of HO-1 activity or knockdown of HO-1 in the murine macrophage RAW264.7 cells abolished the TauCl-induced phagocytosis, whereas the overexpression of HO-1 augmented the phagocytic ability of macrophages. Moreover, peritoneal macrophages isolated from HO-1 null mice failed to mediate TauCl-induced phagocytosis. Our results suggest that TauCl potentiates phagocytic activity of macrophages through upregulation of HO-1 expression., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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12. Both nitric oxide and nitrite prevent homocysteine-induced endoplasmic reticulum stress and subsequent apoptosis via cGMP-dependent pathway in neuronal cells.
- Author
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Jeong SO, Son Y, Lee JH, Choi SW, Kim SH, Cheong YK, Chung HT, and Pae HO
- Subjects
- Animals, Apoptosis drug effects, Cell Line, Endoplasmic Reticulum Stress drug effects, Mice, Neurons cytology, Neurons drug effects, Neuroprotective Agents administration & dosage, Signal Transduction drug effects, Signal Transduction physiology, Apoptosis physiology, Cyclic GMP metabolism, Endoplasmic Reticulum Stress physiology, Homocysteine administration & dosage, Neurons physiology, Nitric Oxide administration & dosage, Nitrites administration & dosage
- Abstract
Growing evidence indicates that endoplasmic reticulum (ER) stress and/or ER stress-mediated apoptosis may play a role in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease. The present study investigated the effects of non-cytotoxic concentrations of nitric oxide (NO) and nitrite, a metabolite of NO, on ER stress and ER stress-mediated apoptosis in Neuro-2a cells exposed to homocysteine (Hcy), an endogenous ER stress inducer. Hcy induced ER stress, as confirmed by inositol-requiring enzyme 1α (IRE1α) phosphorylation and X-box-binding protein-1 (Xbp1) mRNA splicing as well as C/EBP homologous protein (CHOP) expression, and apoptosis, as verified by Annexin V-positive cells. Surprisingly, non-cytotoxic NO (S-nitrosoglutathione) and nitrite markedly reduced Hcy-induced IRE1α phosphorylation, Xbp1 mRNA splicing, CHOP expression, and Annexin V-positive cells, indicating the cytoprotection of NO and nitrite against Hcy-induced ER stress and apoptosis. Moreover, inhibition of sGC/cGMP pathway abolished the cytoprotective effects of NO and nitrite, whereas cellular elevation of cGMP levels mimicked the cytoprotective actions of NO and nitrite. These findings provide the first evidence showing that both NO and nitrite can reduce ER stress and subsequent apoptosis via NO-sGC-cGMP pathway in neuronal cells and suggesting that NO and/or nitrite may have therapeutic value in the treatment of ER stress-associated neurodegenerative diseases., (Copyright © 2017. Published by Elsevier Inc.)
- Published
- 2017
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13. Tristetraprolin mediates anti-inflammatory effects of carbon monoxide on lipopolysaccharide-induced acute lung injury.
- Author
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Joe Y, Kim SK, Chen Y, Yang JW, Lee JH, Cho GJ, Park JW, and Chung HT
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- Acute Lung Injury chemically induced, Acute Lung Injury pathology, Animals, Cytokines analysis, Cytokines genetics, Female, Gene Expression Regulation, Lipopolysaccharides adverse effects, Male, Mice, Mice, Knockout, RNA, Messenger genetics, RNA, Messenger metabolism, Tristetraprolin drug effects, Tristetraprolin genetics, Acute Lung Injury drug therapy, Anti-Inflammatory Agents pharmacology, Carbon Monoxide pharmacology, Tristetraprolin metabolism
- Abstract
Low-dose inhaled carbon monoxide is reported to suppress inflammatory responses and exhibit a therapeutic effect in models of lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the precise mechanism by which carbon monoxide confers protection against ALI is not clear. Tristetraprolin (TTP; official name ZFP36) exerts anti-inflammatory effects by enhancing decay of proinflammatory cytokine mRNAs. With the use of TTP knockout mice, we demonstrate here that the protection by carbon monoxide against LPS-induced ALI is mediated by TTP. Inhalation of carbon monoxide substantially increased the pulmonary expression of TTP. carbon monoxide markedly enhanced the decay of mRNA-encoding inflammatory cytokines, blocked the expression of inflammatory cytokines, and decreased tissue damage in LPS-treated lung tissue. Moreover, knockout of TTP abrogated the anti-inflammatory and tissue-protective effects of carbon monoxide in LPS-induced ALI. These results suggest that carbon monoxide-induced TTP mediates the protective effect of carbon monoxide against LPS-induced ALI by enhancing the decay of mRNA encoding proinflammatory cytokines., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2015
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14. Antagonistic crosstalk between SIRT1, PARP-1, and -2 in the regulation of chronic inflammation associated with aging and metabolic diseases.
- Author
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Chung HT and Joe Y
- Abstract
Current studies have indicated the association of chronic sterile inflammation (inflammation in the absence of pathogens) with the pathogenesis of age-related and metabolic diseases. The inflammation is under the control of transcription factor NF-κB through an antagonistic crosstalk between SIRT1, PARP-1, and -2 signaling pathways. The transcriptional activity of NF-κB is increased in various tissues with aging and metabolic abnormalities and is related with various aging and metabolic diseases such as Alzheimer's disease, diabetes, and osteoporosis. Furthermore, NF-κB activation with chronic inflammation is connected with many known life span and metabolic regulators including DNA damage, obesity, SIRT, and PARP. Thus, the crossroads between PARP and SIRT signaling pathways represent efficient therapeutic targets for extending health span without metabolic diseases.
- Published
- 2014
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15. Pretreatment with CO-releasing molecules suppresses hepcidin expression during inflammation and endoplasmic reticulum stress through inhibition of the STAT3 and CREBH pathways.
- Author
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Shin DY, Chung J, Joe Y, Pae HO, Chang KC, Cho GJ, Ryter SW, and Chung HT
- Subjects
- Animals, Antimicrobial Cationic Peptides genetics, Antimicrobial Cationic Peptides metabolism, Blotting, Western, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Cyclic AMP Response Element-Binding Protein genetics, Cyclic AMP Response Element-Binding Protein metabolism, Hepcidins, Humans, Inflammation drug therapy, Inflammation metabolism, Interleukin-6 genetics, Interleukin-6 metabolism, Iron metabolism, Liver Neoplasms drug therapy, Liver Neoplasms metabolism, Liver Neoplasms pathology, Male, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Phosphorylation drug effects, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, STAT3 Transcription Factor genetics, STAT3 Transcription Factor metabolism, Signal Transduction, Antimetabolites pharmacology, Antimicrobial Cationic Peptides antagonists & inhibitors, Carbon Monoxide pharmacology, Cyclic AMP Response Element-Binding Protein antagonists & inhibitors, Endoplasmic Reticulum Stress drug effects, Inflammation pathology, STAT3 Transcription Factor antagonists & inhibitors
- Abstract
The circulating peptide hormone hepcidin maintains systemic iron homeostasis. Hepcidin production increases during inflammation and as a result of endoplasmic reticulum (ER) stress. Elevated hepcidin levels decrease dietary iron absorption and promote iron sequestration in reticuloendothelial macrophages. Furthermore, increased plasma hepcidin levels cause hypoferremia and the anemia associated with chronic diseases. The signal transduction pathways that regulate hepcidin during inflammation and ER stress include the IL-6-dependent STAT-3 pathway and the unfolded protein response-associated cyclic AMP response element-binding protein-H (CREBH) pathway, respectively. We show that carbon monoxide (CO) suppresses hepcidin expression elicited by IL-6- and ER-stress agents by inhibiting STAT-3 phosphorylation and CREBH maturation, respectively. The inhibitory effect of CO on IL-6-inducible hepcidin expression is dependent on the suppressor of cytokine signaling-3 (SOCS-3) protein. Induction of ER stress in mice resulted in increased hepatic and serum hepcidin. CO administration inhibited ER-stress-induced hepcidin expression in vivo. Furthermore, ER stress caused iron accumulation in splenic macrophages, which could be prevented by CO. Our findings suggest novel anti-inflammatory therapeutic applications for CO, as well as therapeutic targets for the amelioration of anemia in the hypoferremic condition associated with chronic inflammatory and metabolic diseases.
- Published
- 2012
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16. Heme oxygenase-1 comes back to endoplasmic reticulum.
- Author
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Kim HP, Pae HO, Back SH, Chung SW, Woo JM, Son Y, and Chung HT
- Subjects
- Animals, Heme Oxygenase-1 genetics, Humans, Mice, Organelles enzymology, Unfolded Protein Response, Endoplasmic Reticulum enzymology, Heme Oxygenase-1 metabolism, Stress, Physiological
- Abstract
Originally identified as a rate-limiting enzyme for heme catabolism, heme oxygenase-1 (HO-1) has expanded its roles in anti-inflammation, anti-apoptosis and anti-proliferation for the last decade. Regulation of protein activity by location is well appreciated. Even though multiple compartmentalization of HO-1 has been documented, the functional implication of this enzyme at these subcellular organelles is only partially elucidated. In this review we discuss the endoplasmic reticulum (ER)-residing HO-1 and its cytoprotective activity against ER stress., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2011
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17. Role of heme oxygenase in preserving vascular bioactive NO.
- Author
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Pae HO, Son Y, Kim NH, Jeong HJ, Chang KC, and Chung HT
- Subjects
- Animals, Heme Oxygenase-1 genetics, Humans, Nitric Oxide antagonists & inhibitors, Nitric Oxide biosynthesis, Nitric Oxide Synthase Type III metabolism, Protein Kinases metabolism, Transcription Factors metabolism, Heme Oxygenase-1 metabolism, Muscle, Smooth, Vascular metabolism, Nitric Oxide metabolism
- Abstract
Beyond its vasodilator role, vascular nitric oxide (NO), which is synthesized by endothelial NO synthase (eNOS) via its activation, has been shown to play a number of other beneficial roles in the vascular system; it inhibits proliferation of vascular smooth muscle cells, prevents platelet aggregation, and regulates endothelial apoptosis. Such beneficial roles have been shown to be implicated in the regulation of endothelial functions. A loss of NO bioavailability that may result either from decreased eNOS expression and activity or from increased NO degradation is associated with endothelial dysfunction, a key factor in the development of vascular diseases. Heme oxygenase-1 (HO-1), an inducible enzyme, catalyzes the oxidative degradation of heme to free iron, carbon monoxide, and biliverdin, the latter being subsequently converted into bilirubin. In the vascular system, HO-1 and heme degradation products perform important physiological functions, which are ultimately linked to the protection of vascular cells. Studies have shown that HO-1 and heme degradation products exert vasodilatory, antioxidant, anti-inflammatory, antiproliferative and anti-apoptotic effects on vascular cells. Interestingly, these effects of HO-1 and its by-products are similar, at least in part, to those of eNOS-derived NO; this similarity may prompt investigators to study a possible relationship between eNOS-derived NO and HO-1 pathways. Many studies have been reported, and accumulating evidence suggests that HO-1 and heme degradation products can improve vascular function, at least in part, by compensating for the loss of NO bioavailability. This paper will provide the possible pathway explaining how HO-1 and heme degradation products can preserve vascular NO., (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Published
- 2010
- Full Text
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18. Hydrogen peroxide induces heme oxygenase-1 and dentin sialophosphoprotein mRNA in human pulp cells.
- Author
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Min KS, Lee HJ, Kim SH, Lee SK, Kim HR, Pae HO, Chung HT, Shin HI, Lee SK, and Kim EC
- Subjects
- Blotting, Western, Cell Differentiation, Cell Survival drug effects, Cells, Cultured, Cytoprotection, Dental Pulp cytology, Dental Pulp metabolism, Heme Oxygenase-1 biosynthesis, Humans, MAP Kinase Signaling System drug effects, Odontoblasts cytology, Oxidative Stress, Phosphoproteins biosynthesis, RNA, Messenger biosynthesis, Reverse Transcriptase Polymerase Chain Reaction, Sialoglycoproteins, Tooth Bleaching adverse effects, Dental Pulp drug effects, Extracellular Matrix Proteins biosynthesis, Heme Oxygenase-1 physiology, Hydrogen Peroxide toxicity, Oxidants toxicity
- Abstract
Although the induction of heme oxygenase-1 (HO-1) by hydrogen peroxide (H2O2) has been reported, the HO-1 and odontoblastic differentiation-inducing effects against H2O2 have not been clarified in human pulp cells. In this study, we investigated whether HO-1 is involved in the protective mechanisms against the cytotoxic effects of H2O2 by using a cell viability assay, and we examined the production of dentin sialophosphoprotein (DSPP) and other mineralization markers by using reverse transcriptase-polymerase chain reaction in human pulp cells. H2O2 decreased cell viability but increased HO-1 and DSPP expression in a concentration- and time-dependent manner. Antioxidants and inhibitors of HO-1, phosphatidylinositol-3'-kinase, extracellular signal-regulated kinase, and p38 mitogen-activated protein kinase blocked H2O2-induced cytotoxicity and the expression of HO-1 and DSPP mRNA in pulp cells. These data suggest that the induction of HO-1 by H2O2 in pulp cells plays a protective role against the cytotoxic effects of H2O2 and stimulates DSPP expression, resulting in premature odontoblast differentiation through pathways that involve phosphatidylinositol-3'-kinase, p38, and extracellular signal-regulated kinase.
- Published
- 2008
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19. Tranilast, an orally active anti-allergic drug, up-regulates the anti-inflammatory heme oxygenase-1 expression but down-regulates the pro-inflammatory cyclooxygenase-2 and inducible nitric oxide synthase expression in RAW264.7 macrophages.
- Author
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Pae HO, Jeong SO, Koo BS, Ha HY, Lee KM, and Chung HT
- Subjects
- Administration, Oral, Animals, Anti-Allergic Agents administration & dosage, Anti-Inflammatory Agents administration & dosage, Cell Line, Cyclooxygenase 2 metabolism, Cytokines antagonists & inhibitors, Cytokines metabolism, Down-Regulation, Inflammation, Lipopolysaccharides pharmacology, Macrophages enzymology, Macrophages immunology, Mice, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Nitric Oxide Synthase Type II metabolism, Up-Regulation, ortho-Aminobenzoates administration & dosage, Anti-Allergic Agents pharmacology, Anti-Inflammatory Agents pharmacology, Heme Oxygenase-1 metabolism, Macrophages drug effects, ortho-Aminobenzoates pharmacology
- Abstract
Tranilast (N-[3',4'-dimethoxycinnamonyl] anthranilic acid), an orally active anti-allergic drug, is reported to exert the anti-inflammatory effects, but the underlying mechanisms that could explain the anti-inflammatory actions of tranilast remain largely unknown. Here, we found that tranilast induces heme oxygenase-1 (HO-1) expression through the extracellular signal-regulated kinase-1/2 (ERK1/2) pathway in RAW264.7 macrophages. Tranilast suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide (NO) synthase (iNOS) expression, and thereby reduced COX-2-derived prostaglandin E(2) (PGE(2)) and iNOS-derived NO production in lipopolysaccharide (LPS)-stimulated macrophages. Similarly, tranilast diminished tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) production. Interestingly, the effects of tranilast on LPS-induced PGE(2), NO, TNF-alpha, and IL-1beta production were partially reversed by the HO-1 inhibitor tin protoporphyrin, suggesting that tranilast-induced HO-1 expression is at least partly responsible for the resulting anti-inflammatory effects of the drug. Thus, HO-1 expression via ERK1/2 activation may be at least one of the possible mechanisms explaining the anti-inflammatory actions of tranilast.
- Published
- 2008
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20. Involvement of mitogen-activated protein kinases and nuclear factor-kappa B activation in nitric oxide-induced interleukin-8 expression in human pulp cells.
- Author
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Min KS, Kim HI, Chang HS, Kim HR, Pae HO, Chung HT, Hong SH, Shin HI, Hong CU, Lee SK, and Kim EC
- Subjects
- Blotting, Western, Cells, Cultured, Dental Pulp cytology, Dental Pulp drug effects, Enzyme-Linked Immunosorbent Assay, Extracellular Signal-Regulated MAP Kinases antagonists & inhibitors, Extracellular Signal-Regulated MAP Kinases metabolism, Humans, I-kappa B Proteins metabolism, NF-kappa B antagonists & inhibitors, Nitric Oxide pharmacology, Nitric Oxide Donors pharmacology, Nitroprusside pharmacology, Phosphorylation, Pulpitis metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors, p38 Mitogen-Activated Protein Kinases metabolism, Dental Pulp metabolism, Interleukin-8 biosynthesis, MAP Kinase Signaling System physiology, NF-kappa B metabolism, Nitric Oxide physiology
- Abstract
Objective: This study examined the effect of nitric oxide (NO) on interleukin-8 (IL-8) production and the involvement of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappaB) signaling pathways in primary cultured human pulp cells., Study Design: IL-8 production was measured using enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. MAPK activation and IkappaB degradation and phosphorylation were determined by western blotting., Results: Sodium nitroprusside (SNP), an NO donor, has increased IL-8 secretion and mRNA expression in a dose- and time-dependent manner. SNP induced the phosphorylation of p38 MAPK and extracellular-regulated kinase (ERK), degradation and phosphorylation of IkappaB, and activation of NF-kappaB. Furthermore, inhibition of the ERK, p38, and NF-kappaB pathways blocked SNP-induced IL-8 secretion., Conclusion: Human pulp cells showed NO-induced IL-8 expression via the MAPK and NF-kappaB pathways, which may play an important role in the inflammatory responses of pulp and periapical lesions.
- Published
- 2008
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21. Concurrent expression of heme oxygenase-1 and p53 in human retinal pigment epithelial cell line.
- Author
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Lee SY, Jo HJ, Kim KM, Song JD, Chung HT, and Park YC
- Subjects
- Cell Line, Gene Expression Regulation physiology, Humans, Heme Oxygenase-1 metabolism, Pigment Epithelium of Eye metabolism, Signal Transduction physiology, Tumor Suppressor Protein p53 metabolism
- Abstract
Heme oxygenase-1 (HO-1) is a stress-responsive protein that is known to regulate cellular functions such as cell proliferation, inflammation, and apoptosis. Here, we investigated the effects of HO activity on the expression of p53 in the human retinal pigment epithelium (RPE) cell line ARPE-19. Cobalt protoporphyrin (CoPP) induced the expression of both HO-1 and p53 without significant toxicity to the cells. In addition, the blockage of HO activity with the iron chelator DFO or with HO-1 siRNA inhibited the CoPP-induced expression of p53. Similarly, zinc protoporphyrin (ZnPP), an inhibitor of HO, suppressed p53 expression in ARPE-19 cells, although ZnPP increased the level of HO-1 protein while inhibiting HO activity. Also, CoPP-induced p53 expression was not affected by the formation of reactive oxygen species (ROS). Based on these results, we conclude that HO activity is involved in the regulation of p53 expression in a ROS-independent mechanism, and also suggest that the expression of p53 in ARPE-19 cells is associated with heme metabolites such as biliverdin/bilirubin, carbon monoxide, and iron produced by the activity of HO.
- Published
- 2008
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22. Wogonin suppresses TARC expression induced by mite antigen via heme oxygenase 1 in human keratinocytes. Suppressive effect of wogonin on mite antigen-induced TARC expression.
- Author
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Lee BS, Shim SM, Heo J, Pae HO, Seo BY, Han SY, Sohn DH, Jang SI, and Chung HT
- Subjects
- Animals, Antigens, Dermatophagoides immunology, Antigens, Dermatophagoides pharmacology, Cell Line, Transformed, Chemokine CCL17, Dermatitis, Atopic immunology, Dermatophagoides farinae, Drugs, Chinese Herbal chemistry, Drugs, Chinese Herbal pharmacology, Extracellular Signal-Regulated MAP Kinases metabolism, Flavanones chemistry, Gene Expression drug effects, Gene Expression immunology, Heme Oxygenase-1 metabolism, Humans, In Vitro Techniques, Keratinocytes cytology, Phosphorylation drug effects, Scutellaria baicalensis, Chemokines, CC genetics, Dermatitis, Atopic drug therapy, Flavanones pharmacology, Heme Oxygenase-1 genetics, Keratinocytes drug effects, Keratinocytes immunology
- Abstract
Background: Mite antigen, extract from Dermatophagoides farinae in house dust, is a well-known causative agent of atopy or allergic diseases, which involves many inflammatory cytokines/chemokines expression. Heme oxygenase 1 (HO1) has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types., Objective: The aim of this study was to investigate the possible mechanism by which wogonin, a natural product isolated from Scutellaria baicalensis, inhibited the mite antigen-induced chemokine expression in human keratinocytes, HaCaT cells., Methods: The level of chemokine expression was measured by reverse transcription-polymerase chain reaction (RT-PCR) and signaling study was performed by Western blot analysis., Results: The mite antigen-induced thymus- and activation-regulated chemokine (TARC/CCL17) expression in a dose-dependent manner via extracellular signal-regulated kinase (ERK) activation. However, it did not affect the expression of other chemokines including macrophage-derived chemokine (MDC/CCL22), RANTES, and IL-8. Interestingly, wogonin significantly suppressed the mite antigen-induced TARC expression via the induction of HO1. This suppression was completely restored by HO1 siRNA, suggesting a direct role of HO1 for the suppressive effect. Furthermore, exogenous CO, but not other end products of HO1 activity, also suppressed the mite antigen-induced TARC expression., Conclusion: Wogonin induces HO1 expression, which in turn HO1 and/or CO suppresses TARC expression induced by mite antigen in human HaCaT cells.
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- 2007
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23. Curcumin induces pro-apoptotic endoplasmic reticulum stress in human leukemia HL-60 cells.
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Pae HO, Jeong SO, Jeong GS, Kim KM, Kim HS, Kim SA, Kim YC, Kang SD, Kim BN, and Chung HT
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- Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Blotting, Western, Caspase Inhibitors, Caspases, Initiator metabolism, Curcumin analogs & derivatives, Curcumin chemistry, Dose-Response Relationship, Drug, Endoplasmic Reticulum metabolism, HL-60 Cells, Humans, Leukemia, Promyelocytic, Acute genetics, Leukemia, Promyelocytic, Acute metabolism, Leukemia, Promyelocytic, Acute pathology, Molecular Structure, RNA, Small Interfering genetics, Transcription Factor CHOP genetics, Transcription Factor CHOP metabolism, Transfection, Apoptosis drug effects, Curcumin pharmacology, Endoplasmic Reticulum drug effects
- Abstract
Curcumin has been shown to induce apoptosis in many cancer cells. However, the molecular mechanism(s) responsible for curcumin-induced apoptosis is not well understood and most probably involves several pathways. In HL-60 cells, curcumin induced apoptosis and endoplasmic reticulum (ER) stress as evidenced by the survival molecules such as phosphorylated protein kinase-like ER-resident kinase, phosphorylated eukaryotic initiation factor-2alpha, glucose-regulated protein-78, and the apoptotic molecules such as caspase-4 and CAAT/enhancer binding protein homologous protein (CHOP). Inhibition of caspase-4 activity by z-LEVD-FMK, blockage of CHOP expression by small interfering RNA, and treatment with salubrinal, an ER inhibitor, significantly reduced curcumin-induced apoptosis. Removing two double bonds in curcumin, which was speculated to form Michael adducts with thiols in secretory proteins, resulted in a loss of the ability of curcumin to induce apoptosis as well as ER stress. Thus, the present study shows that curcumin-induced apoptosis is associated with its ability to cause ER stress.
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- 2007
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24. 3-Hydroxyanthranilic acid, one of L-tryptophan metabolites, inhibits monocyte chemoattractant protein-1 secretion and vascular cell adhesion molecule-1 expression via heme oxygenase-1 induction in human umbilical vein endothelial cells.
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Pae HO, Oh GS, Lee BS, Rim JS, Kim YM, and Chung HT
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- 3-Hydroxyanthranilic Acid metabolism, Antioxidants metabolism, Atherosclerosis immunology, Atherosclerosis metabolism, Bilirubin metabolism, Bilirubin pharmacology, Endothelium, Vascular cytology, Endothelium, Vascular metabolism, Free Radical Scavengers metabolism, Gene Expression Regulation, Enzymologic drug effects, Heme Oxygenase-1 metabolism, Humans, NF-E2-Related Factor 2 metabolism, NF-kappa B metabolism, Response Elements physiology, Tryptophan metabolism, Tumor Necrosis Factor-alpha metabolism, Umbilical Veins cytology, Vascular Cell Adhesion Molecule-1 metabolism, 3-Hydroxyanthranilic Acid pharmacology, Chemokine CCL2 metabolism, Endothelium, Vascular drug effects, Free Radical Scavengers pharmacology, Heme Oxygenase-1 genetics, Vascular Cell Adhesion Molecule-1 genetics
- Abstract
Heme oxygenase (HO)-1 is important in the vascular system, and its genetic or pharmacological induction in endothelium would be effective for the prevention and treatment of atherosclerosis. The naturally occurring antioxidant 3-hydroxyanthranilic acid (HA), one of l-tryptophan metabolites formed in vivo along the metabolic route known as the kynurenine pathway during inflammation or infection, was found to induce HO-1 expression and to stimulate nuclear translocation of NF-E2 related factor 2 (Nrf2) in human umbilical vein endothelial cells (HUVECs). Pre-treatment with HA inhibited the secretion of monocyte chemoattractant protein (MCP)-1, the expression of vascular cell adhesion molecule (VCAM)-1 and the activation of transcriptional nuclear factor (NF)-kappaB in HUVECs stimulated with tumor necrosis factor-alpha, the major pro-inflammatory cytokine causing endothelial inflammation. Interestingly, the observed anti-inflammatory effects of HA were mimicked by a HO-1 inducer, cobalt protoporphyrin, and bilirubin, one of HO-1 enzymatic products, but abolished in the presence of a HO-1 inhibitor, tin protoporphyrin. Based on our findings, we suggest that Nrf2-dependent HO-1 expression induced by HA inhibits MCP-1 secretion, VCAM-1 expression and NF-kappaB activation associated with vascular injury and inflammation in atherosclerosis.
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- 2006
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25. Hydrogen sulfide potentiates interleukin-1beta-induced nitric oxide production via enhancement of extracellular signal-regulated kinase activation in rat vascular smooth muscle cells.
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Jeong SO, Pae HO, Oh GS, Jeong GS, Lee BS, Lee S, Kim du Y, Rhew HY, Lee KM, and Chung HT
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- Animals, Aorta, Thoracic cytology, Butadienes pharmacology, Cells, Cultured, Enzyme Activation, Enzyme Inhibitors pharmacology, Nitric Oxide Synthase Type II metabolism, Nitriles pharmacology, Rats, Hydrogen Sulfide pharmacology, Interleukin-1 metabolism, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Muscle, Smooth, Vascular cytology, Muscle, Smooth, Vascular enzymology, Nitric Oxide metabolism
- Abstract
Hydrogen sulfide (H(2)S) and nitric oxide (NO) are endogenously synthesized from l-cysteine and l-arginine, respectively. They might constitute a cooperative network to regulate their effects. In this study, we investigated whether H(2)S could affect NO production in rat vascular smooth muscle cells (VSMCs) stimulated with interleukin-1beta (IL-1beta). Although H(2)S by itself showed no effect on NO production, it augmented IL-beta-induced NO production and this effect was associated with increased expression of inducible NO synthase (iNOS) and activation of nuclear factor (NF)-kappaB. IL-1Beta activated the extracellular signal-regulated kinase 1/2 (ERK1/2), and this activation was also enhanced by H(2)S. Inhibition of ERK1/2 activation by the selective inhibitor U0126 inhibited IL-1beta-induced NF-kappaB activation, iNOS expression, and NO production either in the absence or presence of H(2)S. Our findings suggest that H(2)S enhances NO production and iNOS expression by potentiating IL-1beta-induced NF-kappaB activation through a mechanism involving ERK1/2 signaling cascade in rat VSMCs.
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- 2006
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26. Carbon monoxide mediates heme oxygenase 1 induction via Nrf2 activation in hepatoma cells.
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Lee BS, Heo J, Kim YM, Shim SM, Pae HO, Kim YM, and Chung HT
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- Active Transport, Cell Nucleus, Animals, Carcinoma, Hepatocellular, Cell Line, Tumor, Cell Nucleus metabolism, Heme Oxygenase-1 biosynthesis, Hepatocytes drug effects, Hepatocytes metabolism, Humans, Liver Neoplasms, MAP Kinase Signaling System, Promoter Regions, Genetic, Rats, Response Elements, Up-Regulation, Carbon Monoxide pharmacology, Gene Expression Regulation, Enzymologic, Heme Oxygenase-1 genetics, Hepatocytes enzymology, NF-E2-Related Factor 2 metabolism, Transcriptional Activation
- Abstract
Carbon monoxide (CO) and nitric oxide (NO) are two gas molecules which have cytoprotective functions against oxidative stress and inflammatory responses in many cell types. Currently, it is known that NO produced by nitric oxide synthase (NOS) induces heme oxygenase 1 (HO1) expression and CO produced by the HO1 inhibits inducible NOS expression. Here, we first show CO-mediated HO1 induction and its possible mechanism in human hepatocytes. Exposure of HepG2 cells or primary hepatocytes to CO resulted in dramatic induction of HO1 in dose- and time-dependent manner. The CO-mediated HO1 induction was abolished by MAP kinase inhibitors (MAPKs) but not affected by inhibitors of PI3 kinase or NF-kappaB. In addition, CO induced the nuclear translocation and accumulation of Nrf2, which suppressed by MAPKs inhibitors. Taken together, we suggest that CO induces Nrf2 activation via MAPKs signaling pathways, thereby resulting in HO1 expression in HepG2 cells.
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- 2006
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27. Catalase protects cardiomyocytes via its inhibition of nitric oxide synthesis.
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Chae HJ, Ha KC, Kim DS, Cheung GS, Kwak YG, Kim HM, Kim YM, Pae HO, Chung HT, Chae SW, and Kim HR
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- Animals, Biopterins analogs & derivatives, Biopterins pharmacology, Catalase antagonists & inhibitors, Heart Ventricles cytology, Interferon-Stimulated Gene Factor 3 toxicity, Interleukin-1 toxicity, Myocytes, Cardiac cytology, NF-kappa B metabolism, Nitric Oxide biosynthesis, Peroxynitrous Acid metabolism, Rats, Rats, Wistar, Reactive Oxygen Species metabolism, Tumor Necrosis Factor-alpha toxicity, Apoptosis drug effects, Catalase pharmacology, Cytokines toxicity, Myocytes, Cardiac drug effects, Nitric Oxide antagonists & inhibitors
- Abstract
Nitric oxide (NO) has been reported to play an important role as an effector molecule in cytokine signal transduction in cardiomyocytes. A treatment of neonatal rat ventricular cardiomyocytes with interleukin-1 beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) induces apoptosis via an NO-dependent pathway. However, cardiomyocytes were more resistant to NO-dependent cell death in the presence of catalase, while producing inducible nitric oxide synthase. This paper reports that catalase stimulates the NF-kappaB-binding affinity. However, the NO synthase activity is abolished by the addition of catalase, suggesting that H(2)O(2) is involved in NO synthesis in a posttranslation state. The catalase-induced inhibition of NO was partially but significantly reversed by H(4)B, an important cofactor of NO synthesis. Treatment of myocytes with IL-1beta, TNF-alpha, and IFN-gamma induced a significant increase in the formation of peroxynitrite, and a pretreatment with catalase was found to quench the production of peroxynitrite. This paper shows that the catalase activity was significantly down-regulated by H(4)B in a concentration-dependent manner. The treatment of H(4)B induced reactive oxygen species (ROS) release in cardiac cell system. These results suggest that catalase interferes with NO and peroxynitrite production as well as with the related apoptosis of cardiomyocytes. This study also shows that the catalase-induced inhibition of NO release may be reversed by H(4)B by the release of ROS.
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- 2006
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28. Critical role of heme oxygenase-1 in Foxp3-mediated immune suppression.
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Choi BM, Pae HO, Jeong YR, Kim YM, and Chung HT
- Subjects
- CD4-Positive T-Lymphocytes immunology, Cell Proliferation, DNA-Binding Proteins genetics, DNA-Binding Proteins immunology, Forkhead Transcription Factors, Gene Expression Regulation, Leukemic, Heme Oxygenase (Decyclizing) genetics, Heme Oxygenase-1, Humans, Immune Tolerance immunology, Jurkat Cells, Membrane Proteins, Receptors, Interleukin-2 immunology, Transfection, DNA-Binding Proteins metabolism, Heme Oxygenase (Decyclizing) metabolism
- Abstract
Foxp3, which encodes the transcription factor scurfin, is indispensable for the development and function of CD4(+)CD25(+) regulatory T cells (Treg). Recent data suggest conversion of peripheral CD4(+)CD25(-) nai ve T cells to CD4(+)CD25(+) Treg by acquisition of Foxp3 through costimulation with TCR and TGF-beta or forced expression of the gene. One critical question is how Foxp3 causes T cells to become regulatory. In the present work, we demonstrate that Foxp3 can induce heme oxygenase-1 (HO-1) expression and subsequently such regulatory phenotypes as the suppression of nontransfected cells in a cell-cell contact-dependent manner as well as impaired proliferation and production of cytokines upon stimulation in Jurkat T cells. Moreover, we confirm the expression of both Foxp3 and HO-1 in peripheral CD4(+)CD25(+) Treg and suppressive function of the cells are relieved by the inhibition of HO-1 activity. In summary, we demonstrate that Foxp3 induces HO-1 expression and HO-1 engages in Foxp3-mediated immune suppression.
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- 2005
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29. Induction of heme oxygenase-1 is involved in anti-proliferative effects of paclitaxel on rat vascular smooth muscle cells.
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Choi BM, Kim YM, Jeong YR, Pae HO, Song CE, Park JE, Ahn YK, and Chung HT
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- Animals, Cells, Cultured, Gene Expression Regulation, Enzymologic drug effects, Heme Oxygenase (Decyclizing) metabolism, Heme Oxygenase-1, Mitogen-Activated Protein Kinases metabolism, Muscle, Smooth, Vascular cytology, Muscle, Smooth, Vascular drug effects, Phosphorylation, RNA, Messenger genetics, Rats, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic drug effects, Cell Division drug effects, Heme Oxygenase (Decyclizing) genetics, Muscle, Smooth, Vascular enzymology, Paclitaxel pharmacology
- Abstract
In this study, we evaluated the possibility that the anti-proliferative effects of paclitaxel on vascular smooth muscle cells (VSMCs) of the rat might be due to the induction of HO-1 gene expression. Treatment of the cells with paclitaxel resulted in marked time- and dose-dependent inductions of HO-1 mRNA, followed by corresponding increases in HO-1 protein expression and HO enzymatic activities. Furthermore, paclitaxel rapidly activated the JNK, ERK, and p38 mitogen-activated protein kinase pathways. A specific inhibitor of JNK, SP600125, abolished paclitaxel-induced HO-1 mRNA expression, whereas PD98059, a specific inhibitor of ERK, and SB203580, a specific inhibitor of p38, had no significant effect. Finally, the suppression of platelet-derived growth factor induced VSMC proliferation was abolished by the HO inhibitor, ZnPP, as well as by the CO scavenger, hemoglobin. These results demonstrated that paclitaxel induces the expression of HO-1 via the JNK pathway in VSMC and that HO-1 expression might be responsible for the anti-proliferative effect of paclitaxel on VSMC.
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- 2004
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30. 3-Hydroxyanthranilic acid, one of metabolites of tryptophan via indoleamine 2,3-dioxygenase pathway, suppresses inducible nitric oxide synthase expression by enhancing heme oxygenase-1 expression.
- Author
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Oh GS, Pae HO, Choi BM, Chae SC, Lee HS, Ryu DG, and Chung HT
- Subjects
- Animals, Cell Line, Dose-Response Relationship, Drug, Enzyme Activation drug effects, Heme Oxygenase-1, Indoleamine-Pyrrole 2,3,-Dioxygenase, Interferon-gamma pharmacology, Lipopolysaccharides pharmacology, Macrophages drug effects, Membrane Proteins, Mice, Nitric Oxide Synthase Type II, Signal Transduction physiology, 3-Hydroxyanthranilic Acid pharmacology, Heme Oxygenase (Decyclizing) metabolism, Macrophages metabolism, Nitric Oxide Synthase metabolism, Tryptophan metabolism, Tryptophan Oxygenase metabolism
- Abstract
Inducible nitric oxide (NO) synthase (iNOS), heme oxygenase (HO)-1, and indoleamine 2,3-dioxygenase (IDO) are simultaneously expressed in murine macrophages stimulated with interferon (IFN)-gamma and lipopolysaccharide (LPS). NO produced by iNOS suppresses IDO expression and also induces HO-1 expression. The antioxidant 3-hydroxyanthranilic acid (HA), one of metabolites of tryptophan via IDO pathway, has been previously reported to suppress iNOS expression. Because HO-1 expression can suppress iNOS expression, we investigated whether HA could suppress iNOS expression by affecting HO-1 expression in murine RAW 264.7 macrophages stimulated with IFN-gamma plus LPS. Treatment with exogenous HA dose-dependently suppressed iNOS expression and coincidently enhanced HO-1 expression. This suppressive effect of HA on iNOS expression was reversed by blocking HO-1 activity, and proven to be due to carbon monoxide (CO) produced by HO-1. In addition, either blocking of iNOS activity or addition of exogenous CO further enhanced IDO expression and activity. These results show for the first time that HA is able to suppress iNOS expression by enhancing HO-1 expression, thereby resulting in further increases in IDO expression and activity.
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- 2004
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31. Analysis of the polymorphisms in eotaxin gene family and their association with asthma, IgE, and eosinophil.
- Author
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Chae SC, Lee YC, Park YR, Shin JS, Song JH, Oh GJ, Hong ST, Pae HO, Choi BM, and Chung HT
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- Adult, Asthma blood, Chemokine CCL11, Chromosome Mapping methods, Female, Gene Frequency, Genetic Testing methods, Humans, Korea epidemiology, Leukocyte Count, Male, Polymorphism, Genetic, Polymorphism, Single Nucleotide genetics, Statistics as Topic, Asthma epidemiology, Asthma genetics, Chemokines, CC genetics, Eosinophils cytology, Genetic Predisposition to Disease epidemiology, Genetic Predisposition to Disease genetics, Immunoglobulin E blood
- Abstract
The eotaxin gene family (eotaxin, eotaxin-2, and eotaxin-3) has been implicated in the recruitment of eosinophils, basophiles, and Th2 lymphocytes that is a central aspect of allergic diseases such as asthma. To determine whether the single nucleotide polymorphisms (SNPs) of eotaxin gene family are associated with susceptibility to asthma, we scanned 225 asthma patients and 294 non-asthmatic controls using the direct sequencing method. We further investigated the relationships among each SNP, eosinophils, and serum total IgE levels in asthma patients. Eleven SNPs were identified in the eotaxin gene family. We found that EoB179T > C (P = 0.0001), EoB275C > T (P = 0.018) of the eotaxin-2 and EoA2497T > G (P = 0.003) of the eotaxin-3 were significantly associated with the susceptibility of asthma. Furthermore, our data demonstrated for the first time that EoA2497T > G (P = 0.005) is related to serum total IgE level while EoA77C > T (P = 0.035) and EoA2497T > G (P = 0.033) are related to the peripheral blood eosinophil counts in asthma. Our results suggest that the polymorphisms of the eotaxin gene family are associated with the susceptibility of asthma and Eotaxin-3 might play the critical role for the recruitment of eosinophils and the maintenance of IgE levels.
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- 2004
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32. Scopoletin suppresses pro-inflammatory cytokines and PGE2 from LPS-stimulated cell line, RAW 264.7 cells.
- Author
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Kim HJ, Jang SI, Kim YJ, Chung HT, Yun YG, Kang TH, Jeong OS, and Kim YC
- Subjects
- Animals, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents therapeutic use, Cell Line drug effects, Cyclooxygenase 2, Dinoprostone metabolism, Dose-Response Relationship, Drug, Interleukin-1 metabolism, Interleukin-6 metabolism, Isoenzymes metabolism, Lipopolysaccharides, Mice, Prostaglandin-Endoperoxide Synthases metabolism, Scopoletin administration & dosage, Scopoletin therapeutic use, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents pharmacology, Artemisia, Macrophages drug effects, Macrophages metabolism, Phytotherapy, Scopoletin pharmacology
- Abstract
Scopoletin (1-50 microg/ml) inhibited the release of PGE2, TNF-alpha, IL-1beta and IL-6 and suppressed the expression of COX-2 in a concentration-dependent manner. These results suggest that scopoletin might suppress the production of such pro-inflammatory cytokines and exert inhibitory activity on LPS-induced PGE2 production through the depression of COX-2 expression., (Copyright 2004 Elsevier B.V.)
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- 2004
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33. The exon 4 variations of Tim-1 gene are associated with rheumatoid arthritis in a Korean population.
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Chae SC, Song JH, Shim SC, Yoon KS, and Chung HT
- Subjects
- Adult, Arthritis, Rheumatoid blood, C-Reactive Protein metabolism, Case-Control Studies, Exons, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genotype, Hepatitis A Virus Cellular Receptor 1, Humans, Korea, Male, Middle Aged, Odds Ratio, Rheumatoid Factor blood, Arthritis, Rheumatoid genetics, Membrane Glycoproteins genetics, Receptors, Virus genetics
- Abstract
The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, TIM-1, is considered as a membrane protein that is associated with the development of Th2 biased immune responses and selectively expressed on Th2 cells. In the present study, we analyzed the association of genotype and allele frequencies between rheumatoid arthritis (RA) patients and the controls without RA using large samples size at 5383_5397del and 5509_5511delCAA variations of Tim-1 gene. We further investigated the relationships among these variations to C-reactive protein (CRP) and rheumatoid factor (RF) levels in RA patients. Although these factors were not associated with exon 4 variations in RA patients, the genotype and allele frequencies of 5383_5397del variation site (P = 0.015 and 0.014, respectively) as well as 5509_5511delCAA variation site (P = 0.0002 and 0.0001, respectively) in RA patients were significantly different from those in the non-RA controls. Our results strongly suggest that the variations of Tim-1 exon 4 might be associated with the susceptibility to RA.
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- 2004
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34. The association of the exon 4 variations of Tim-1 gene with allergic diseases in a Korean population.
- Author
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Chae SC, Song JH, Lee YC, Kim JW, and Chung HT
- Subjects
- Case-Control Studies, Eosinophils cytology, Exons, Gene Frequency, Genetic Testing, Genetic Variation, Genotype, Hepatitis A Virus Cellular Receptor 1, Humans, Hypersensitivity blood, Hypersensitivity genetics, Immunoglobulin E blood, Korea epidemiology, Leukocyte Count, Reference Values, Risk Assessment methods, Risk Factors, Statistics as Topic, Asthma blood, Asthma genetics, Dermatitis, Atopic blood, Dermatitis, Atopic genetics, Genetic Predisposition to Disease epidemiology, Membrane Glycoproteins genetics, Receptors, Virus genetics
- Abstract
The family of T-cell immunoglobulin domain and mucin domain (TIM) proteins is identified to be expressed on T cells. A member of Tim family, TIM-1, is considered as a membrane protein that is associated with the development of Th2 biased immune responses and may be selectively expressed on Th2 cells. In the present study, we analyzed the association of allele and genotype frequencies between asthma or atopy patients and the controls without asthma and atopy using large sample size at 5383_5397del and 5509_5511delCAA variations of Tim-1 gene. Although the allele frequency of 5509_5511delCAA variation in asthma was not significantly different (P=0.085), the genotype of 5509_5511delCAA variation in asthma was significantly associated with the susceptibility to asthma (P=0.037). The genotype and allele frequencies of 5383_5397del variation in atopic dermatitis were significantly different from those in the non-asthmatic and non-atopic controls (P=0.005 and P=0.002, respectively). Our results strongly suggest that the 5383_5397del variation site of Tim-1 exon 4 might be associated with atopic dermatitis susceptibility.
- Published
- 2003
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35. The absolute configuration of prunioside A from Spiraea prunifolia and biological activities of related compounds.
- Author
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Oh H, Shin H, Oh GS, Pae HO, Chai KY, Chung HT, and Lee HS
- Subjects
- Animals, Cell Line, Dose-Response Relationship, Drug, Glycosides isolation & purification, Macrophages drug effects, Macrophages metabolism, Magnetic Resonance Spectroscopy, Mice, Molecular Conformation, Nitric Oxide biosynthesis, Nitric Oxide Synthase biosynthesis, Nitric Oxide Synthase Type II, Stereoisomerism, Terpenes isolation & purification, Glycosides chemistry, Glycosides pharmacology, Spiraea chemistry, Terpenes chemistry, Terpenes pharmacology
- Abstract
The stereochemistry of prunioside A isolated from Spiraea prunifolia was determined by chemical transformations and NMR spectral data analysis. The configurations at C-5 and C-6 were determined to be 5S and 6R by application of the modified Mosher's method, CD analysis, and 13C NMR spectroscopic data analysis of an acetonide derivative. Other compounds related to prunioside A have inhibitory effects on the synthesis of nitric oxide in LPS-stimulated macrophage-like RAW 264.7 cells.
- Published
- 2003
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36. Catalposide protects Neuro 2A cells from hydrogen peroxide-induced cytotoxicity via the expression of heme oxygenase-1.
- Author
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Moon MK, Choi BM, Oh GS, Pae HO, Kim JD, Oh H, Oh CS, Kim DH, Rho YD, Shin MK, Lee HS, and Chung HT
- Subjects
- Animals, Bilirubin metabolism, Blotting, Western, Carbon Monoxide metabolism, Cell Line, Cell Survival drug effects, Heme Oxygenase-1, Iron metabolism, Membrane Proteins, Mice, Oxidative Stress drug effects, Diuretics pharmacology, Glucosides pharmacology, Heme Oxygenase (Decyclizing) biosynthesis, Hydrogen Peroxide antagonists & inhibitors, Hydrogen Peroxide toxicity, Neurons drug effects, Neuroprotective Agents pharmacology, Oxidants toxicity
- Abstract
Catalposide, the major iridoid glycoside isolated from the stem bark of Catalpa ovata G. Don (Bignoniaceae) has been shown to possess anti-microbial, anti-tumoral, and anti-inflammatory properties. Heme oxygenase-1 (HO-1) is a stress response protein and is known to play a protective role against the oxidative injury. In this study, we examined whether catalposide could protect Neuro 2A cells, a kind of neuronal cell lines, from oxidative damage through the induction of HO-1 protein expression and HO activity. The treatment of the cells with catalposide resulted in dose- and time-dependent up-regulations of both HO-1 protein expression and HO activity. Catalposide protected the cells from hydrogen peroxide-induced cell death. The protective effect of catalposide on hydrogen peroxide-induced cell death was abrogated by zinc protoporphyrin IX (ZnPP IX), a HO inhibitor. Additional experiments revealed the involvement of CO in the cytoprotective effect of catalposide-induced HO-1. These results indicate that catalposide is a potent inducer of HO-1 and HO-1 induction is responsible for the catalposide-mediated cytoprotection against oxidative damage.
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- 2003
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37. Differential expressions of heme oxygenase-1 gene in CD25- and CD25+ subsets of human CD4+ T cells.
- Author
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Pae HO, Oh GS, Choi BM, Chae SC, and Chung HT
- Subjects
- CD28 Antigens metabolism, CD4-Positive T-Lymphocytes physiology, Cell Division physiology, Gene Expression Regulation, Enzymologic, Heme Oxygenase-1, Humans, Immunomagnetic Separation, Jurkat Cells, Membrane Proteins, CD4-Positive T-Lymphocytes enzymology, Heme Oxygenase (Decyclizing) genetics, Heme Oxygenase (Decyclizing) metabolism, Receptors, Interleukin-2 metabolism, T-Lymphocyte Subsets enzymology
- Abstract
Growing evidence suggests that the immunomodulatory heme oxygenase-1 (HO-1) may have an important role in regulating T-cell responses. In this study, we investigated whether CD4(+)CD25(-) and CD4(+)CD25(+) T cells of human CD4(+) subpopulation could differentially express HO-1. Our results obtained from qualitative reverse transcriptase-polymerase chain reaction and quantitative flow cytometry analyses revealed that the CD4(+)CD25(+) T cells constitutively express HO-1 and that T cell stimulation with plate-bound anti-CD3 in combination with soluble anti-CD28 not only induced HO-1 gene expression in the CD4(+)CD25(-) T cells but also up-regulated HO-1 gene expression in the CD4(+)CD25(+) T cells. Our further studies showed that CD28 signal alone was enough to induce HO-1 expression and CD3 signal, of which signal alone did not induce HO-1 expression, was required at least for full HO-1 expression in both CD25(-) and CD25(+) subsets of human CD4(+) T cells. In addition, transfection of human Jurkat T cells with HO-1 suppressed the cellular proliferation, and this effect was reversed by zinc protoporphyrin, a specific HO competitive inhibitor. Taken together, we have first reported that human CD4(+)CD25(+) regulatory T cells constitutively express HO-1 and that HO-1 inhibits Jurkat T cell proliferation.
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- 2003
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38. Pentoxifylline protects L929 fibroblasts from TNF-alpha toxicity via the induction of heme oxygenase-1.
- Author
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Oh GS, Pae HO, Moon MK, Choi BM, Yun YG, Rim JS, and Chung HT
- Subjects
- Blotting, Western, Catalysis, Cell Line, Heme Oxygenase-1, Enzyme Induction drug effects, Fibroblasts drug effects, Heme Oxygenase (Decyclizing) biosynthesis, Pentoxifylline pharmacology, Tumor Necrosis Factor-alpha physiology
- Abstract
Tumor necrosis factor-alpha (TNF-alpha) is recognized as a principal mediator of a variety of inflammatory conditions. Pentoxifylline (PTX), which can inhibit cellular TNF-alpha synthesis, also attenuates the toxic effect of TNF-alpha. However, the mechanism underlying PTX-induced cytoprotection is unknown. Heme oxygenase 1 (HO-1) is an enzyme which degrades heme into biliverdin, free iron, and carbon monoxide (CO). This enzyme has recently been shown to have anti-inflammatory and cytoprotective effects. In this study, we investigated whether protection by PTX against TNF-alpha-mediated toxicity could be related to its ability to induce HO-1 expression and HO activity in L929 cells. PTX in the range of 0.1-1.0mM significantly induced HO-1 expression and the resulting HO activity. Pre-incubation of L929 cells with either PTX or the HO activator hemin resulted in the protection of the cells against TNF-alpha-mediated toxicity. Zinc protoporphyrin, a specific HO competitive inhibitor, abrogated the protective effect of PTX. Hemoglobin, a scavenger of CO, reversed the protective effect of PTX. A cytoprotection comparable to PTX was observed when the cells were treated with the CO-releasing compound tricarbonyldichlororuthenium(II) dimer. These results suggest that HO-1 expression and the ensuing formation of the HO metabolite CO may be a novel pathway by which PTX protects L929 cells from TNF-alpha-mediated toxicity.
- Published
- 2003
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39. Involvement of p38 MAP kinase during iron chelator-mediated apoptotic cell death.
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Kim BS, Yoon KH, Oh HM, Choi EY, Kim SW, Han WC, Kim EA, Choi SC, Kim TH, Yun KJ, Kim EC, Lyou JH, Nah YH, Chung HT, Cha YN, and Jun CD
- Subjects
- Animals, Apoptosis drug effects, Caspase 3, Caspase 8, Caspase 9, Caspases metabolism, Cytochrome c Group metabolism, Deferoxamine antagonists & inhibitors, Enzyme Activation, Enzyme Inhibitors pharmacology, HL-60 Cells, Humans, Imidazoles pharmacology, Intracellular Membranes drug effects, Intracellular Membranes physiology, Iron antagonists & inhibitors, Jurkat Cells enzymology, Jurkat Cells metabolism, Membrane Potentials drug effects, Membrane Potentials physiology, Mice, Mitochondria drug effects, Mitochondria physiology, Pyridines pharmacology, Signal Transduction drug effects, Signal Transduction physiology, p38 Mitogen-Activated Protein Kinases, Apoptosis physiology, Deferoxamine pharmacology, Iron metabolism, Iron Chelating Agents pharmacology, Mitogen-Activated Protein Kinases metabolism
- Abstract
Iron is an essential element for the neoplastic cell growth, and iron chelators have been tested for their potential anti-proliferative and cytotoxic effects. To determine the mechanism of cell death induced by iron chelators, we explored the pathways of the three structurally related mitogen-activated protein (MAP) kinase subfamilies during apoptosis induced by iron chelators. We report that the chelator deferoxamine (DFO) strongly activates both p38 MAP kinase and extracellular signal-regulated kinase (ERK) at an early stage of incubation, but slightly activates c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) at a late stage of incubation. Among three MAP kinase blockers used, however, the selective p38 MAP kinase inhibitor SB203580 could only protect HL-60 cells from chelator-induced cell death, indicating that p38 MAP kinase serves as a major mediator of apoptosis induced by iron chelator. DFO also caused release of cytochrome c from mitochondria and induced activation of caspase 3 and caspase 8. Interestingly, treatment of HL-60 cells with SB203580 greatly abolished cytochrome c release, and activation of caspase 3 and caspase 8. Collectively, the current study reveals that p38 MAP kinase plays an important role in iron chelator-mediated cell death of HL-60 cells by activating downstream apoptotic cascade that executes cell death pathway.
- Published
- 2002
- Full Text
- View/download PDF
40. Germination inhibitory constituents from Erigeron annuus.
- Author
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Oh H, Lee S, Lee HS, Lee DH, Lee SY, Chung HT, Kim TS, and Kwon TO
- Subjects
- Flowers chemistry, Inhibitory Concentration 50, Lactuca drug effects, Magnetic Resonance Spectroscopy, Mass Spectrometry, Molecular Structure, Seeds drug effects, Asteraceae chemistry, Germination drug effects, Plant Extracts pharmacology
- Abstract
(5-Butyl-3-oxo-2,3-dihydrofuran-2-yl)-acetic acid was isolated from the flowers of Erigeron annuus as one of four germination inhibitory constituents. Its structure was determined by analysis of MS and NMR spectroscopic data. Three known compounds, 3-hydroxy-pyran-4-one, 4-hydroxycinnamic acid, and 3,4-dihydroxycinnamic acid methyl ester were also identified as active constituents. These compounds showed 50% inhibitory effects (IC(50)) on the germination of lettuce seed at concentrations of 2.13+/-0.03, 12.85+/-0.56, 4.97+/-0.24, and 4.87+/-0.25 mM, respectively. 4-Hydroxybenzoic acid was used as a positive control, displaying an IC(50) value of 4.02+/-0.39 mM.
- Published
- 2002
- Full Text
- View/download PDF
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