Cyclosporine A regulate oxidative stress-induced apoptosis in cardiomyocytes: Mechanisms via ROS generation, iNOS and Hsp70

Huei Wen Chen, Chiang Ting Chien, Sung Liang Yu, Yuan Teh Lee, Wen Jone Chen*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

92 引文 斯高帕斯(Scopus)

摘要

1. Previous study suggested that cyclosporine A (CsA) could partially reduce ischaemia/reperfusion-induced injury in isolated heart, but the mechanism was still unclear. In this study, the possible mechanisms of cyclosporine A in regulating oxidative stress-induced cardiomyocyte apoptosis were examined. 2. Morphological (cell shrinkage, apoptotic body formation, and DNA fragmentation) and biochemical (annexin-V staining for exposed phosphatidylserine residues) evidences showed that both hydrogen peroxide (H 2O 2) and hypoxia/reoxygenation could induce apoptotic change in the embryonal rat heart myoblast-derived cells (H9c2). These effects were inhibited by pre-treatment with CsA at concentration of 0.01-1.0 μM for 24 h, but were increased with 10.0 μM CsA. 3. While examining the mechanisms of CsA in protecting cardiomyocyte apoptosis, we found that the collapse of mitochondria membrane potential (Δψm) induced by oxidative stress was partially reversed by CsA (0.01-1.0 μM). 4. Compared to the control, CSA at the concentration of 0.1 and 10.0 μM significantly increased the level of intracellular reactive oxygen species (ROS) to 117.2±12.4% and 234.4±9.3%, respectively. Co-incubating with the antioxidant, ascorbic acid (10.0 μM), could partially reduce the protective effect of CsA (0.01-1.0 μM) and the toxic effect of 10.0 μM CsA. 5. Pre-treatment with CsA at concentration of 0.01-1.0 μM for 24 h produced up-regulation of heat shock protein 70 (Hsp 70), inducible nitric oxide synthase (iNOS) and also induced NO production, indicating that these factors might be associated with the cell protective effects of CsA. 6. These results suggest that CsA could protect the oxidative stress-induced cardiomyocyte apoptosis not only by preventing the loss of Δψm in mitochondria, but also through ROS generation, Hsp70, and iNOS up-regulation.

原文英語
頁(從 - 到)771-781
頁數11
期刊British Journal of Pharmacology
137
發行號6
DOIs
出版狀態已發佈 - 2002 十一月
對外發佈

ASJC Scopus subject areas

  • 藥理

指紋

深入研究「Cyclosporine A regulate oxidative stress-induced apoptosis in cardiomyocytes: Mechanisms via ROS generation, iNOS and Hsp70」主題。共同形成了獨特的指紋。

引用此