title: Upregulation of arginase activity contributes to intracellular ROS production induced by high glucose in H9c2 cells.
abstract: Arginase is upregulated in some tissues under diabetes states. Arginase can compete with nitroxide synthase (NOS) for the common substrate L-arginine and thus increases oxidative stress by NOS uncoupling. We want to analyze whether arginase is upregulated and contribute to oxidative stress in H9c2 cells during high glucose treatment. H9c2 cells were cultured in normal or high glucose DMEM. Arginase activity increased in parallel with increased cell death and oxidative stress. Arginase inhibitor N ω-hydroxy-nor-l-arginine (nor-NOHA) and NOS inhibitor N ω-nitro-l-arginine methyl ester (L-NAME) could reverse these effects. Despite of upregulated NOS activity, NO production was impaired which could be preserved by nor-NOHA, suggesting a decreased substrate availability of NOS due to increased arginase activity. L-arginine supplementation decreased superoxide production while it could not protect cells from death. Upregulated arginase activity in H9c2 treated with high glucose can cause NOS uncoupling and subsequently reactive oxygen species augmentation and cell death. These findings suggest that arginase will be a novel therapeutic target for treatment of diabetic cardiomyopathy.
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing, P. R. China.
authors.forename: Chuan-Bo
authors.initials: CB
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing, P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing, P. R. China.
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing, P. R. China.
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University Nanjing, P. R. China.
authors.forename: Qing-Ping
authors.initials: QP
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001119:Arginase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001120:Arginine / Q000494:pharmacology; D002460:Cell Line; D058065:Diabetic Cardiomyopathies / Q000201:enzymology* / Q000473:pathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D004791:Enzyme Inhibitors; D017382:Reactive Oxygen Species; D013481:Superoxides; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase; D005947:Glucose
keywords: Arginase; NOS uncoupling; cardiomyocyte; diabetes; oxidative stress