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Mechanisms of apoptosis of endothelial and vascular smooth muscle cells by reactive oxygen species -Relationship with the initiation of arteriosclerosis-

活性氧引起的内皮和血管平滑肌细胞凋亡的机制-与动脉硬化起始的关系-

基本信息

批准号：
08670174
负责人：
SUZUKI Keiichiro
金额：
$ 1.34万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670174/
关键词：
endothelial cells apoptosis glutathione SOD reactive oxygen species 抗酸化物質 NO (peroxynitrite)

项目摘要

The Apoptosis of various cells requires inducers including free radicals. Endothelial cells and vascular smooth muscle cells are generally considered to be resistant to apoptosis but recent studies suggest that such changes in these cells relate to atherosclerotic changes. Snake venom generates intracellular peroxides in endothelial cells, which leads to apoptosis. This cell type play an important role in atherosclerosis and its normal resistance to apoptosis may be related to its anti-oxidant levels.When the intracellular glutathione and Cu, Zn-SOD levels were decreased by the sddition of buthionine sulfoximine (BSO) and diethyldithiocarbamate (DDC), respectively, the apoptosis of endothelial cells was accelerated. The addition of acetylated LDL and glucose enhanced the cytotoxicity of snake venom whereas pretreatment with tumor necrosis factor (TNF) or phorbol ester (TPA), which increases the Mn-SOD level, prevented the apoptosis of endothelialcells. These data suggest that peroxides enhance apoptosis whereas several anti-oxidative agents, such as glutathione and SOD,are protective. The induction of apoptosis by peroxides of endothelial cells may be related to initiation of atheroscrelosis.

各种细胞的凋亡需要自由基等诱导剂。内皮细胞和血管平滑肌细胞通常被认为对细胞凋亡有抵抗力，但最近的研究表明这些细胞的这种变化与动脉粥样硬化的变化有关。蛇毒在内皮细胞中产生细胞内过氧化物，导致细胞凋亡。该细胞类型在动脉粥样硬化中起重要作用，其正常的抗凋亡能力可能与其抗氧化水平有关。当分别加入丁硫氨酸亚砜亚胺（BSO）和二乙基二硫代氨基甲酸酯（DDC）降低细胞内谷胱甘肽和Cu、Zn-SOD水平时，内皮细胞凋亡加速。添加乙酰化 LDL 和葡萄糖增强了蛇毒的细胞毒性，而肿瘤坏死因子 (TNF) 或佛波酯 (TPA) 预处理可增加 Mn-SOD 水平，防止内皮细胞凋亡。这些数据表明，过氧化物可增强细胞凋亡，而谷胱甘肽和 SOD 等几种抗氧化剂则具有保护作用。内皮细胞过氧化物诱导细胞凋亡可能与动脉粥样硬化的发生有关。