Korean J Physiol Pharmacol.  2019 Nov;23(6):519-528. 10.4196/kjpp.2019.23.6.519.

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

Affiliations
  • 1Department of Biochemistry, Dongguk University College of Medicine, Gyeongju 38066, Korea. wanlee@dongguk.ac.kr
  • 2Channelopathy Research Center, Dongguk University College of Medicine, Goyang 10326, Korea.

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 Hâ‚‚Oâ‚‚ 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.

Keyword

Antioxidant; Catalase; Glutathione peroxidase; Mitochondrial DNA; Myoblasts; Reactive oxygen species

MeSH Terms

Catalase
DNA, Mitochondrial*
Glutathione
Glutathione Disulfide
Glutathione Peroxidase
Hand
Homeostasis
Myoblasts*
Oxidation-Reduction
Oxidative Stress*
Reactive Oxygen Species
Catalase
DNA, Mitochondrial
Glutathione
Glutathione Disulfide
Glutathione Peroxidase
Reactive Oxygen Species
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