PR-39 and PR-11 peptides inhibit ischemia-reperfusion injury by blocking proteasome-mediated IκBα degradation
PR-39 and PR-11 peptides inhibit ischemia-reperfusion injury by blocking proteasome-mediated IκBα degradation
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DOI：
10.1152/ajpheart.2001.281.6.h2612
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发表时间：
2001-12-01
影响因子：
4.8
通讯作者：
Post, MJ
中科院分区：
文献类型：
--
作者：
Bao, JL;Sato, K;Post, MJ
PR-39抑制蛋白酶体介导的I kappaBα降解，可能对缺血再灌注损伤有保护作用。我们在大鼠心脏缺血-再灌流模型中研究了PR-39及其截短形式PR-11，以及缺乏阻止I kappaBα降解能力的突变体PR-11AAA。分别于缺血30min和再灌流2 4h后测定心功能、心肌梗死面积、中性粒细胞浸润和髓过氧化物酶活性。再灌流时心肌内注射10nmol/kg PR-39或PR-11使心肌梗死面积分别缩小65%和57%，24 h后血压、左心室收缩压、舒张力和舒缩力(+/-dp/dt)均较空白对照组明显改善。中性粒细胞浸润减少，髓过氧化物酶活性降低，细胞间黏附分子-1和血管细胞黏附分子-1表达减少。因此，PR-39和PR-11对大鼠在体心肌缺血再灌注损伤有明显的抑制作用。这种作用是通过抑制I-kappaBα降解和随后抑制核因子-kappaB依赖的黏附分子来实现的。活性序列位于前11个氨基酸，提示寡肽治疗有可能作为血管重建的辅助手段。
PR-39 inhibits proteasome-mediated I kappaB alpha degradation and might protect against ischemia-reperfusion injury. We studied PR-39, its truncated form PR-11, and a mutant PR-11AAA, which lacks the ability to prevent I kappaB alpha degradation, in a rat heart ischemia-reperfusion model. After 30 min of ischemia and 24 h of reperfusion, cardiac function, infarct size, neutrophil infiltration, and myeloperoxidase activity were measured. Intramyocardial injection of 10 nmol/kg PR-39 or PR-11 at the time of reperfusion reduced infarct size by 65% and 57%, respectively, which improved blood pressure, left ventricular systolic pressure, and relaxation and contractility (+/-dP/dt) compared with vehicle controls 24 h later. Neutrophil infiltration, myeloperoxidase activity, and the expression of intercellular adhesion molecule-1 and vascular cell adhesion molecule 1 were reduced. Thus PR-39 and PR-11 effectively inhibit myocardial ischemia-reperfusion injury in the rat in vivo. This effect is mediated by inhibition of I kappaB alpha degradation and subsequent inhibition of nuclear factor-kappaB-dependent adhesion molecules. The active sequence is located in the first 11 amino acids, suggesting a potential for oligopeptide therapy as an adjunct to revascularization.