线粒体
磷脂过氧化氢谷胱甘肽过氧化物酶
缺血
GPX4
化学
转基因小鼠
脂质过氧化
转基因
再灌注损伤
心功能曲线
内科学
内分泌学
谷胱甘肽
谷胱甘肽过氧化物酶
生物化学
抗氧化剂
生物
医学
酶
心力衰竭
基因
作者
Erinne R. Dabkowski,Courtney Williamson,John M. Hollander
标识
DOI:10.1016/j.freeradbiomed.2008.06.021
摘要
Ischemia/reperfusion (I/R) injury elicits damage to mitochondria. Antioxidants provide protection from I/R-induced mitochondrial damage. The goal of this study was to determine the impact of mitochondria-specific overexpression of GPx4 (PHGPx) on cardiac function following I/R. Transgenic mice were created in which PHGPx was overexpressed solely in the mitochondrion (mPHGPx). MPHGPx and littermate control hearts were subjected to global no-flow ischemia (20 min) followed by reflow reperfusion (30, 60, and 90 min). Following I/R, mPHGPx hearts possessed significantly better rates of contraction, developed pressures, and peak-systolic pressures as compared to controls (P < 0.05). No differences were observed in rates of relaxation or end-diastolic pressures. Lipid peroxidation was significantly lower in mitochondria from mPHGPx hearts as compared to controls, following I/R (P < 0.05). Electron transport chain (ETC) complex I, III, and IV activities were significantly higher in mPHGPx hearts as compared to controls, following I/R (P < 0.05). MPHGPx overexpression enhanced ETC complex I, III, and IV activities in subsarcolemmal mitochondria (SSM; P < 0.05), and ETC complex I and III activities in interfibrillar mitochondria (IFM; P < 0.05) following I/R. These results indicate that mitochondria-specific GPx4 overexpression protects cardiac contractile function and preserves ETC complex activities following I/R. These results provide further rationale for the use of mPHGPx as a therapeutic protectant.
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