Exogenous BH4/Bcl-2 peptide reverts coronary endothelial cell apoptosis induced by oxidative stress
Exogenous BH4/Bcl-2 peptide reverts coronary endothelial cell apoptosis induced by oxidative stress
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DOI：
10.1159/000077408
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发表时间：
2004-01-01
影响因子：
1.7
通讯作者：
Ziche, M
中科院分区：
文献类型：
--
作者：
Cantara, S;Donnini, S;Ziche, M
背景资料：血管内皮细胞在暴露于活性氧（ROS）（包括过氧化氢和超氧自由基）时发生凋亡。ROS被认为是缺血再灌注损伤期间小血管损伤和动脉粥样硬化期间动脉损伤的原因。过氧化氢诱导的细胞凋亡是通过抑制Bcl-xl活性和caspase-3和caspase-9活化介导的。Bcl-2家族成员的BH 4结构域负责其抗凋亡活性。Bcl-2和Bcl-xl的BH 4结构域抑制细胞色素c释放和线粒体膜电位的损失。方法和结果：本课题的目的是研究Bcl-2的细胞渗透衍生物（BH 4肽）对暴露于应激条件下的内皮细胞的抗凋亡作用。将BH 4肽与细胞渗透性肽达特缀合，并在血清饥饿和过氧化氢处理的条件下应用于内皮细胞。TAT-BH 4降低caspase-3活性并防止凋亡性细胞死亡。结论：TAT-BH 4肽对ROS诱导的内皮细胞凋亡具有保护作用。版权所有（C）2004 S. Karger AG，巴塞尔。
Background: Vascular endothelium undergoes apoptosis when exposed to reactive oxygen species (ROS), including hydrogen peroxide and superoxide radicals. ROS are believed to be the cause of damage to small vessels during ischemia-reperfusion injury and of arterial damage during atherosclerosis. Hydrogen peroxide-induced apoptosis is mediated through the inhibition of Bcl-xl activity and caspase-3 and caspase-9 activation. The BH4 domain of the Bcl-2 family members is responsible for their antiapoptotic activity. The BH4 domains of Bcl-2 and Bcl-xl inhibit cytochrome c release and the loss of mitochondrial membrane potential. Methods and Results: The purpose of this project was to study the antiapoptotic effect of cell-permeant derivative of Bcl-2 (BH4 peptide) on endothelial cells exposed to stress conditions. BH4 peptide was conjugated to the cell-permeable peptide TAT and was applied to endothelial cells under conditions of serum starvation and hydrogen peroxide treatment. TAT-BH4 reduced caspase-3 activity and prevented apoptotic cell death. Conclusion: Our results indicate that TAT-BH4 peptide can protect endothelial cells from ROS-induced apoptosis. Copyright (C) 2004 S. Karger AG, Basel.