N acetylcysteine induces apoptosis via the mitochondria dependent pathway but not via endoplasmic reticulum stress in H9c2 cells
发布时间：2021-06-02
点击次数：
发表刊物：Mol Med Rep.
关键字：N-acetylcysteine, apoptosis, mitochondria-dependent pathway, endoplasmic reticulum
摘要：N-acetylcysteine (NAC), a precursor of glutathione, is a widely used thiol-containing antioxidant and modulator of the intracellular redox state. Our previous study demonstrated that excess reduced glutathione (GSH) from NAC treatment paradoxically led to a reduction in glutathione redox potential, increased mitochondrial oxidation and caused cytotoxicity at lower reactive oxygen species levels in H9c2 cells. However, no detailed data are available on the molecular mechanisms of NAC-induced cytotoxicity on H9c2 cells. In the present study, it was demonstrated that NAC-induced cytotoxicity towards H9c2 cells was associated with apoptosis. The activation of caspase-9 and −3, and cleavage of procaspase-9 and −3, but not of caspase-8, were involved in NAC-induced apoptosis. The dissipation of mitochondrial transmembrane potential, release of cytochrome c, translocation of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax) to the mitochondria, and the increased ratio of Bax/Bcl-2 mRNA indicated that NAC treatment-induced apoptosis occurred mainly through the mitochondria-dependent pathway. Redox western blot analysis demonstrated that NAC did not disrupt the highly oxidized environment of the endoplasmic reticulum, which was indicated by maintenance of the oxidized form of protein disulfide isomerase, an essential chaperone in the formation of disulfide bond formation in the endoplasmic reticulum. In addition, no significant changes in the expression of binding immunoglobulin protein or C/EBP homologous protein were apparent in the process of NAC-induced apoptosis. Taken together, the present study demonstrated for the first time, to the best of our knowledge, that NAC induced apoptosis via the mitochondria-dependent pathway but not via endoplasmic reticulum stress in H9c2 cells, and the exogenous GSH from NAC did not alter the oxidized milieu of the endoplasmic reticulum.
合写作者：Ke Liu
第一作者：Yuyong Liu
论文类型：基础研究
通讯作者：Nian Wang,Huali Zhang（通讯作者）
学科门类：医学
一级学科：基础医学
期号：2017 Nov;16(5):6626-6633.
是否译文：否
发表时间：2017-09-08
收录刊物：SCI