title: Hyperglycemia induces apoptosis of pancreatic islet endothelial cells via reactive nitrogen species-mediated Jun N-terminal kinase activation.
abstract: Hyperglycemia significantly stimulates pancreatic islet endothelial cell apoptosis; however, the precise mechanisms are not fully understood. In the present study, treating pancreatic islet endothelial (MS-1) cells with high glucose (30mmol/l) but not mannitol significantly increased the number of apoptotic cells as compared with a physiological glucose concentration (5.5mmol/l). Hyperglycemia significantly stimulated the expression of inducible nitric oxide synthase (iNOS) and production of NO and peroxynitrite (ONOO(-)), relevant to MS-1 cell apoptosis. Moreover, induced reactive nitrogen species (RNS) significantly increased the expression of bax, cleaved caspase-3 and poly adenosine diphosphate (ADP)-ribose polymerase (PARP) via JNK activation, but the expression of bcl-2 was not altered. Furthermore, SP600125 (a specific inhibitor of JNK) and 1400W (a specific inhibitor of iNOS) significantly attenuated cell apoptosis induced by high glucose. Therefore, hyperglycemia triggers MS-1 cell apoptosis by activating an intrinsic-dependent apoptotic pathway via RNS-mediated JNK activation.
authors: Department of Endocrinology, Shandong University, Jinan, Shandong, People's Republic of China.
authors: Lei
authors: L
authors: Gong
authors: Fu-Qiang
authors: FQ
authors: Liu
authors: Juan
authors: J
authors: Wang
authors: Xu-Ping
authors: XP
authors: Wang
authors: Xin-Guo
authors: XG
authors: Hou
authors: Yu
authors: Y
authors: Sun
authors: Wei-Dong
authors: WD
authors: Qin
authors: Shu-Jian
authors: SJ
authors: Wei
authors: Yun
authors: Y
authors: Zhang
authors: Li
authors: L
authors: Chen
authors: Ming-Xiang
authors: MX
authors: Zhang
mesh_terms: D000578:Amidines / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001596:Benzylamines / Q000494:pharmacology; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007150:Immunohistochemistry; D007515:Islets of Langerhans / Q000166:cytology; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000578:Amidines; D000873:Anthracenes; C494827:Bax protein, mouse; D001596:Benzylamines; D004791:Enzyme Inhibitors; C104820:N-(3-(aminomethyl)benzyl)acetamidine; D026361:Reactive Nitrogen Species; D051028:bcl-2-Associated X Protein; D030421:Peroxynitrous Acid; C432165:pyrazolanthrone; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D011065:Poly(ADP-ribose) Polymerases; D048031:JNK Mitogen-Activated Protein Kinases; D053148:Caspase 3; D005947:Glucose