Glutathione and K(+) channel remodeling in postinfarction rat heart.
Glutathione and K(+) channel remodeling in postinfarction rat heart.
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梗死后大鼠心脏中谷胱甘肽和 K(+) 通道的重塑。
DOI：
10.1152/ajpheart.00894.2001
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Xu,Zhi
中科院分区：
文献类型：
--
作者：
Rozanski,GeorgeJ;Xu,Zhi
病变脑室的电重构以控制动作电位复极的K+通道下调为特征。最近的研究表明，这种电生理表型的转变涉及氧化应激和细胞内谷胱甘肽(GSH)的变化，谷胱甘肽是氧化还原敏感细胞功能的关键调节因子。本研究观察了谷胱甘肽(GSH)对大鼠心肌梗死(MI)后8wk心肌细胞钾电流的调节作用。对组织提取物的比色分析显示，与对照组相比，心肌梗死后心脏内源性GSH水平显著降低，这表明氧化应激。谷胱甘肽状态的这种变化与谷胱甘肽还原酶和γ-谷氨酰半胱氨酸合成酶活性的显著下降有关。心肌梗死后分离的心肌细胞的电压钳研究表明，外源性GSH或GSH前体N-乙酰半胱氨酸可逆转瞬时外向钾电流(Ito)的下调。二氯乙酸酯也引起Ito的上调，它通过GSH相关的戊糖途径增加糖酵解通量。这种代谢作用被谷胱甘肽还原酶和戊糖途径的抑制剂所阻断。这些数据表明，氧化应激诱导的GSH氧化还原状态的改变在细胞内通道重构中起着重要作用，GSH的稳态受到葡萄糖代谢途径的影响。
Electrical remodeling of the diseased ventricle is characterized by downregulation of K+channels that control action potential repolarization. Recent studies suggest that this shift in electrophysiological phenotype involves oxidative stress and changes in intracellular glutathione (GSH), a key regulator of redox-sensitive cell functions. This study examined the role of GSH in regulating K+currents in ventricular myocytes from rat hearts 8 wk after myocardial infarction (MI). Colorimetric analysis of tissue extracts showed that endogenous GSH levels were significantly less in post-MI hearts compared with controls, which is indicative of oxidative stress. This change in GSH status correlated with significant decreases in activities of glutathione reductase and γ-glutamylcysteine synthetase. Voltage-clamp studies of isolated myocytes from post-MI hearts demonstrated that downregulation of the transient outward K+current (Ito) could be reversed by pretreatment with exogenous GSH orN-acetylcysteine, a precursor of GSH. Upregulation ofItowas also elicited by dichloroacetate, which increases glycolytic flux through the GSH-related pentose pathway. This metabolic effect was blocked by inhibitors of glutathione reductase and the pentose pathway. These data indicate that oxidative stress-induced alteration in the GSH redox state plays an important role inItochannel remodeling and that GSH homeostasis is influenced by pathways of glucose metabolism.
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影响因子：
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DOI：
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