Tumor necrosis factor receptor-associated protein 1 regulates hypoxia-induced apoptosis through a mitochondria-dependent pathway mediated by cytochrome c oxidase subunit II

Burns & Trauma

Hua-pei Song¹  Yue-sheng Huang¹  Yan-ling Lv¹  Dong-xia Zhang¹  Fei Xiang¹  Si-yuan Ma¹ 

[1] 0000 0004 1760 6682, grid.410570.7, Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China;

关键词: Cardiomyocytes;    Hypoxia;    Tumor necrosis factor receptor-associated protein 1;    Cytochrome c oxidase subunit II;    Reactive oxygen species;    Apoptosis;   

DOI  :  10.1186/s41038-019-0154-3

来源: publisher

【 摘 要 】

BackgroundTumor necrosis factor receptor-associated protein 1 (TRAP1) plays a protective effect in hypoxic cardiomyocytes, but the precise mechanisms are not well clarified. The study is aimed to identify the mechanism of TRAP1 on hypoxic damage in cardiomyocytes.MethodsIn this study, the effects of TRAP1 and cytochrome c oxidase subunit II (COXII) on apoptosis in hypoxia-induced cardiomyocytes were explored using overexpression and knockdown methods separately.ResultsHypoxia induced cardiomyocyte apoptosis, and TRAP1 overexpression notably inhibited apoptosis induced by hypoxia. Conversely, TRAP1 silencing promoted apoptosis in hypoxic cardiomyocytes. Further investigation revealed that the proapoptotic effects caused by the silencing of TRAP1 were prevented by COXII overexpression, whereas COXII knockdown reduced the antiapoptotic function induced by TRAP1 overexpression. Additionally, changes in the release of cytochrome c from mitochondria into the cytosol and the caspase-3 activity in the cytoplasm, as well as reactive oxygen species production, were found to be correlated with the changes in apoptosis.ConclusionsThe current study uncovered that TRAP1 regulates hypoxia-induced cardiomyocyte apoptosis through a mitochondria-dependent apoptotic pathway mediated by COXII, in which reactive oxygen species presents as an important component.

【 授权许可】

CC BY