TIR/BB-loop mimetic AS-1 attenuates cardiac ischemia/reperfusion injury via a caveolae and caveolin-3-dependent mechanism.
TIR/BB-loop mimetic AS-1 attenuates cardiac ischemia/reperfusion injury via a caveolae and caveolin-3-dependent mechanism.
复制标题
TIR/BB 环模拟物 AS-1 通过小凹和小凹蛋白 3 依赖性机制减轻心脏缺血/再灌注损伤
DOI：
10.1038/srep44638
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发表时间：
2017-03-14
影响因子：
4.6
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Hu Y;Zhang M;Shen X;Dai G;Ren D;Que L;Ha T;Li C;Xu Y;Ju W;Li Y
AS-1是TIR/BB环模拟物，在心肌缺血/再灌注（I/R）中起保护作用，但其分子机制尚不清楚。肌特异性小窝蛋白3（Cav-3）和小窝蛋白（Caveolae）在心肌保护中起重要作用。本研究的目的是评估我们的假设，小窝和Cav-3是必不可少的AS-1诱导的心脏保护心肌I/R损伤。为了解决这些问题，我们分析了Cav-3在AS-1介导的体内和体外心脏保护中的参与。我们证明，AS-1管理显着减少梗死面积，改善心肌I/R后的心功能和调制膜小窝和Cav-3在心肌中的表达。在体外研究中，AS-1处理防止了H/R损伤引起的Cav-3再分布。与此相反，MCD处理或Cav-3敲低破坏小窝取消了AS-1对H/R诱导的心肌细胞损伤的保护作用。我们的研究结果表明AS-1通过Caveolae和Cav-3依赖性机制减轻心肌I/R损伤。
AS-1, the TIR/BB loop mimetic, plays a protective role in cardiac ischemia/reperfusion (I/R) but the molecular mechanism remains unclear. The muscle specific caveolin3 (Cav-3) and the caveolae have been found to be critical for cardioprotection. This study aimed to evaluate our hypothesis that caveolae and Cav-3 are essential for AS-1-induced cardioprotection against myocardial I/R injury. To address these issues, we analyzed the involvement of Cav-3 in AS-1 mediated cardioprotection bothin vivoandin vitro. We demonstrate that AS-1 administration significantly decreased infarct size, improved cardiac function after myocardial I/R and modulated membrane caveolae and Cav-3 expression in the myocardium. Forin vitrostudies, AS-1 treatment prevented Cav-3 re-distribution induced by H/R injury. In contrast, disruption of caveolae by MCD treatment or Cav-3 knockdown abolished the protection against H/R-induced myocytes injury by AS-1. Our findings reveal that AS-1 attenuates myocardial I/R injury through caveolae and Cav-3 dependent mechanism.