pISSN 1226-4512 eISSN 2093-3827

Article

home Article View

Original Article

Korean J Physiol Pharmacol 2019; 23(6): 519-528

Published online November 1, 2019 https://doi.org/10.4196/kjpp.2019.23.6.519

Copyright © The Korean Journal of Physiology & Pharmacology.

Alteration of mitochondrial DNA content modulates antioxidant enzyme expressions and oxidative stress in myoblasts

Kyung-Ho Min1 and Wan Lee1,2,*

1Department of Biochemistry, Dongguk University College of Medicine, Gyeongju 38066, 2Channelopathy Research Center, Dongguk University College of Medicine, Goyang 10326, Korea

Correspondence to:Wan Lee
E-mail: wanlee@dongguk.ac.kr

Received: August 7, 2019; Revised: September 3, 2019; Accepted: September 3, 2019

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Mitochondrial dysfunction is closely associated with reactive oxygen species (ROS) generation and oxidative stress in cells. On the other hand, modulation of the cellular antioxidant defense system by changes in the mitochondrial DNA (mtDNA) content is largely unknown. To determine the relationship between the cellular mtDNA content and defense system against oxidative stress, this study examined a set of myoblasts containing a depleted or reverted mtDNA content. A change in the cellular mtDNA content modulated the expression of antioxidant enzymes in myoblasts. In particular, the expression and activity of glutathione peroxidase (GPx) and catalase were inversely correlated with the mtDNA content in myoblasts. The depletion of mtDNA decreased both the reduced glutathione (GSH) and oxidized glutathione (GSSG) slightly, whereas the cellular redox status, as assessed by the GSH/GSSG ratio, was similar to that of the control. Interestingly, the steady-state level of the intracellular ROS, which depends on the reciprocal actions between ROS generation and detoxification, was reduced significantly and the lethality induced by H2O2 was alleviated by mtDNA depletion in myoblasts. Therefore, these results suggest that the ROS homeostasis and antioxidant enzymes are modulated by the cellular mtDNA content and that the increased expression and activity of GPx and catalase through the depletion of mtDNA are closely associated with an alleviation of the oxidative stress in myoblasts.

Keywords: Antioxidant, Catalase, Glutathione peroxidase, Mitochondrial DNA, Myoblasts, Reactive oxygen species