![]() Of the levels of GSH through NAC can protect against oxidative Property, and increasing evidence has demonstrated that repletion NAC has attracted interest for its antioxidant Thiol-containing antioxidant and modulator of the intracellular N-acetylcysteine (NAC), a precursor of GSH, is a widely used Recycling via the pentose phosphate pathway and GSH biosynthesis. Glutathione (GSH)/oxidized glutathione (GSSG), is achieved by Maintenance of the glutathione redox couple, reduced However, despite decades of studies on redox biology, the molecularĪnd cellular mechanisms underlying reductive stress remain to be With the dysregulation of glutathione homeostasis and protein Previous findings describing experimental mice found associations The endoplasmic reticulum (ER), which triggers reductive stress and Including dithiothreitol (DTT), are widely used to disruptĭisulfide bond formation and abrogate oxidative protein folding in Increasing number of studies have focused on the deleteriousĮffects of reductive stress in unicellular eukaryotic and mammalianĬells ( 4, 5). Oxidative stress, and is defined as an abnormal increase of Pathophysiology of several diseases ( 2). Is well established that oxidative stress is critical in the Redox homeostasis is essential for normal 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. 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. 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. 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. 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. In the present study, it was demonstrated that NAC‑induced cytotoxicity towards H9c2 cells was associated with apoptosis. However, no detailed data are available on the molecular mechanisms of NAC‑induced cytotoxicity on H9c2 cells. 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. N‑acetylcysteine (NAC), a precursor of glutathione, is a widely used thiol‑containing antioxidant and modulator of the intracellular redox state. ![]()
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