Hyperglycemia induces apoptosis of pancreatic islet endothelial cells via reactive nitrogen species-mediated Jun N-terminal kinase activation
Hyperglycemia induces apoptosis of pancreatic islet endothelial cells via reactive nitrogen species-mediated Jun N-terminal kinase activation
复制标题
高血糖通过活性氮介导的 Jun N 末端激酶激活诱导胰岛内皮细胞凋亡
DOI：
10.1016/j.bbamcr.2011.03.011
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发表时间：
2011-06-01
影响因子：
5.1
通讯作者：
Zhang, Ming-Xiang
中科院分区：
文献类型：
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作者：
Gong, Lei;Liu, Fu-qiang;Zhang, Ming-Xiang
高血糖显著刺激胰岛内皮细胞凋亡，但其确切机制尚不完全清楚。在本研究中，与生理葡萄糖浓度（5.5 mmol/l）相比，高葡萄糖（30 mmol/l）而非甘露醇处理胰岛内皮（MS-1）细胞可显著增加凋亡细胞的数量。高血糖显著刺激诱导型一氧化氮合酶（iNOS）的表达和NO和过氧亚硝酸盐（ONOO(-)）的产生，与MS-1细胞凋亡有关。此外，诱导活性氮（RNS）通过JNK激活显著提高了bax、cleaved caspase-3和聚二磷酸腺苷(ADP)-核糖聚合酶（PARP）的表达，但未改变bcl-2的表达。此外，SP600125 （JNK的特异性抑制剂）和1400W （iNOS的特异性抑制剂）显著减弱高糖诱导的细胞凋亡。因此，高血糖通过rns介导的JNK激活激活内在依赖的凋亡通路，从而触发MS-I细胞凋亡。(C) 2011 Elsevier B.V.版权所有
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 (30 mmol/l) but not mannitol significantly increased the number of apoptotic cells as compared with a physiological glucose concentration (5.5 mmol/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-I cell apoptosis by activating an intrinsic-dependent apoptotic pathway via RNS-mediated JNK activation. (C) 2011 Elsevier B.V. All rights reserved.