Cystine reduces mitochondrial dysfunction in C2C12 myotubes under moderate oxidative stress induced by H2O2.

Abstract

Moderate oxidative stress induces temporal impairment in mitochondrial ATP production. As glutathione (GSH) content is reduced to eliminate oxidative stress by oxidation-reduction reaction, intracellular GSH content is crucial for maintaining mitochondrial function under oxidative stress. GSH precursors such as N-acetyl cysteine (NAC) and cysteine are known to suppress oxidative stress based on the supply of cysteine residues being rate-limiting for GSH synthesis. However, it remains unclear whether cystine (Cys2) can suppress mitochondrial dysfunction under oxidative stress conditions. Therefore, we examined whether Cys2 could attenuate mitochondrial dysfunction under moderate oxidative stress without scavenging reactive oxygen species (ROS) in the medium. C2C12 myotubes were incubated for 120 min in a Cys2-supplemented medium and subsequently exposed to hydrogen peroxide (H2O2). Heme oxygenase-1 (HO-1) gene expression, intracellular cysteine and GSH content, intracellular ATP level, and maximal mitochondrial respiration were assessed. Cys2 treatment significantly increased GSH content in a dose-dependent manner under oxidative stress. Cys2 treatment significantly decreased HO-1 expression induced by H2O2 exposure. In addition, maximal mitochondrial respiration rate was decreased by H2O2 exposure, but improved by Cys2 treatment. In conclusion, Cys2 treatment mitigates oxidative stress-induced mitochondrial dysfunction by maintaining GSH content under moderate oxidative stress without scavenging ROS in the medium.

• Authors: Ami Mizugaki, Hiroyuki Kato, Tomoko Takeda, Yoshiko Inoue, Mai Hasumura, Tatsuya Hasegawa, Hitoshi Murakami
• Journal: Amino acids (Amino Acids) Vol. 54 Issue 8 Pg. 1203-1213 (Aug 2022) ISSN: 1438-2199 [Electronic] Austria
• PMID: 35715620 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Reactive Oxygen Species
• Cystine
• Adenosine Triphosphate
• Hydrogen Peroxide
• Glutathione
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Adenosine Triphosphate (metabolism)
• Apoptosis
• Cystine (pharmacology)
• Glutathione (metabolism)
• Hydrogen Peroxide (metabolism, pharmacology)
• Mitochondria (metabolism)
• Muscle Fibers, Skeletal (metabolism)
• Oxidative Stress
• Reactive Oxygen Species (metabolism)