Mechanism of hydrogen peroxide and hydroxyl free radical-induced intracellular acidification in cultured rat cardiac myoblasts

Mei Lin Wu, Ke Li Tsai, Seu Mei Wang, Jiahn Chun Wu, Bor Sen Wang, Yuan Teh Lee*

*此作品的通信作者

研究成果: Article同行評審

74 引文 斯高帕斯(Scopus)

摘要

After a transient ischemic attack of the cardiac vascular system, reactive oxygen-derived free radicals, including the superoxide (O2-·) and hydroxyl (·OH) radicals can be easily produced during reperfusion. These free radicals have been suggested to be responsible for reperfusion-induced cardiac stunning and reperfusion-induced arrhythmia. Hydrogen peroxide (H2O2) is often used as an experimental source of oxygen-derived free radicals. Using freshly dissociated single rat cardiac myocytes and the rat cardiac myoblast cell line, H9c2, we have shown, for the first time, that an intriguing pH(i) acidification (≃0.24 pH unit) is induced by the addition of 100 μmol/L H2O2 and that this dose is without effect on the intracellular free Ca2+ levels or viability of the cells. Using H9c2 as a model cardiac cell, we have shown that it is the intracellular production of ·OH, and not O2-· or H2O2, that results in this acidification. We have excluded any involvement of (1) the three known cardiac pH(i) regulators (the Na+-H+ exchanger, the Cl--HCO3 exchanger, and the Na+-HCO3 cotransporter), (2) a rise in intracellular Ca2+ levels, and (3) inhibition of oxidative phosphorylation. However, we have found that H2O2-induced acidosis is due to inhibition of the glycolytic pathway, with hydrolysis of intracellular ATP and the resultant intracellular acidification. In cardiac muscle and in skinned cardiac muscle fiber, it has been shown that a small intracellular acidification may severely inhibit contractility. Therefore, the sustained pH(i) decrease caused by hydroxyl radicals may contribute, in some part, to the well-documented impairment of cardiac mechanical function (ie, reperfusion cardiac stunning) seen during reperfusion ischemia.

原文English
頁(從 - 到)564-572
頁數9
期刊Circulation Research
78
發行號4
DOIs
出版狀態Published - 4月 1996

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