The protective effect of N-acetylcysteine on antimycin A-induced respiratory chain deficiency in mesenchymal stem cells

Abstract

Transplantation of mesenchymal stem cells (MSCs) is an effective treatment in tissue injuries though it is limited due to the early death of stem cells within the first few days. The main reason could be a deficiency in the respiratory chain of injured tissues which is linked to the oxidative stress (OS) and disruption of energy metabolism. The disruption in energy metabolism and OS both inhibit the homing of stem cells in the hypoxic micro-environment, however on other hand, the key functions of stem cells are mainly regulated by their cellular redox status and energy metabolism. Because of that, strategies are being developed to improve the bio-functional properties of MSCs, including preconditioning of the stem cells in hypoxic conditions and pretreatment of antioxidants. To achieve this purpose, in this study N-acetylcysteine (NAC) was used for the protection of cells from oxidative stress and the disruption in energy metabolism was induced by Antimycin A (AMA) via blocking the cytochrome C complex. Then several parameters were analyzed, including cell viability/apoptosis, mitochondrial membrane potential, and redox molecular homeostasis. Based on our findings, upon the exposure of the MSCs to the conditions of deficient respiratory chain, the cells failed to scavenge the free radicals, and energy metabolism was disrupted. The use of NAC was found to alleviate the DNA damage, cell apoptosis, and oxidative stress via Nrf2/Sirt3 pathway though without any effect on the mitochondrial membrane potential. It means that antioxidants protect the cells from OS but the problem of ATP metabolism yet remains unresolved in the hypoxic conditions.