Protective effect of gamma-aminobutyric acid against oxidative stress by inducing phase II enzymes in C2C12 myoblast cells

J Food Biochem. 2021 Apr;45(4):e13639. doi: 10.1111/jfbc.13639. Epub 2021 Feb 3.

Abstract

In this study, the cytoprotective effect of gamma-aminobutyric acid (GABA) via inducing phase II enzymes in C2C12 myoblasts was evaluated. The highest concentration of GABA (100 μM) significantly increased the cell viability by approximately 90% in hydrogen peroxide-induced C2C12 cells. The treatment with GABA (100 μM) effectively decreased the glutathione (GSH) depletion and the activities of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). And, reactive oxygen species (ROS) levels were effectively reduced by about 50% in GABA-treated cells. In addition, the protein expression of phase II enzymes, such as NADPH:quinone oxidoreductase 1 and heme oxygenase-1 was significantly increased by GABA treatment. Moreover, GABA treatment increased the nuclear factor erythroid 2-related factor 2 (Nrf2) protein expression in the nucleus of C2C12 myoblasts. Altogether, the results in this study indicate that GABA possesses the cytoprotective effects against oxidative insults by regulating the GSH levels, CAT and SOD activities, ROS scavenging activities, and expression of phase II enzymes through the activation of Nrf2 in C2C12 cells. Hence, this study suggests that the GABA supplementation could be effective in alleviating oxidative stress-induced muscle damage. PRACTICAL APPLICATIONS: GABA exists in the germ and bran layers of rice and is well-known as the inhibitory neurotransmitter in the central nervous system. GABA also has various health beneficial effects, such as preventing chronic alcohol-related diseases and lowering blood pressure. The present study shows the cytoprotective effect of GABA against oxidative stress in C2C12 myoblasts, and suggests that GABA has great potential as a functional food ingredient for attenuating oxidative stress-induced muscle damage.

Keywords: C2C12 myoblasts; NAD(P)H:quinone oxidoreductase 1; gamma-aminobutyric acid; heme oxygenase-1; nuclear factor erythroid 2-related factor; oxidative stress.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Heme Oxygenase-1* / genetics
  • Myoblasts / metabolism
  • Oxidative Stress*
  • Up-Regulation
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • gamma-Aminobutyric Acid
  • Heme Oxygenase-1