Carboxyl terminus of the HSP70-interacting protein (CHIP) is a co-chaperone of HSPs as well as an E3 ubiquitin ligase,and it is the connexin between heat shock proteins and ubiquitin-proteasome system. Recent research discovered that CHIP also possesses an intrinsic chaperone activity that enables it to recognize and bind nonnative proteins independently. CHIP regulates the HSPs expression and activity,and facilitates the client proteins ubiquitination and subsequent proteasome-dependent degradation. CHIP also inhibits apoptosis through MAPKs signaling pathways,and affects eNOS specific activity by means of the effects on Akt. Moreover,CHIP plays an important role in mitochondrial oxidative stress protection. With these above points,this paper reviews the function of CHIP in myocardial ischemia/reperfusion injury.
目的观察蛋白酶体抑制剂MG-132(N-benz0y1 oxycarbonyl(Z)-Leu-Leuleucina1)对急性缺血再灌注大鼠心肌(carboxyl terminus of the Hsc70-interacting protein,CHIP)、HSP70的影响以探讨MG-132的心肌保护机制。方法选择SD大鼠结扎左冠状动脉前降支30min制作心肌缺血再灌注模型,54只大鼠按随机数字表法分入以下各组:治疗(I/R+T)组于再灌注前5min静脉注射MG-132(0.75mg/kg),对照(I/R)组及假手术(Sham)组注射生理盐水,并将I/R组和I/R+T组分为再灌注2、24h及7d亚组(各亚组各8只大鼠),分别用荧光定量PCR法及Western blot法检测CHIP及HSP70的mRNA及蛋白质表达,并进行相关性分析。结果与I/R各时相组相比,I/R+T各时相组CHIP及HSP70的mRNA水平显著升高[(0.87±0.10)vs(0.50±0.06),(0.57±0.07)vs(0.33±0.04),(0.47±0.06)vs(0.19±0.03),P<0.01]。与I/R2、24h组相比I/R+T组CHIP及mRNA水平显著升高[(1.15±0.12)vs(0.57±0.07),(0.81±0.09)vs(0.44±0.06),P<0.01];MG-132上调了I/R+T各时相组HSP70的蛋白质表达,与I/R各组相比,差异均有统计学意义[(1.28±0.16)vs(0.79±0.08),(0.88±0.12)vs(0.58±0.12),(0.9±0.17)vs(0.50±0.09),P<0.01];MG-132上调了I/R+T2、24h组CHIP的蛋白质表达,与I/R2、24h组相比,差异有统计学意义[(1.43±0.15)vs(1.04±0.11),P<0.01;(1.16±0.11)vs(0.96±0.13)],P<0.05)。结论心肌缺血再灌注前适量静注MG-132能显著刺激缺血再灌注大鼠心脏CHIP表达,从而进一步上调HSP70水平,从而保护心肌。
