Role of oxidative stress in hypertrophied myoblasts stimulated by isoproterenol.

OBJECTIVE

Hydrogen peroxide (H(2)O(2)), one of the oxyradical members, has been shown to have insulin-like effects, and endogenous H(2)O(2) may have the ability to improve impaired glucose metabolism. As a mechanism contributing to progression of hypertrophy, we hypothesized that the formation of H(2)O(2) to improve glucose uptake could be an oxidative stress resulting in apoptotic cell death.

METHODS

We used cultured myoblasts (H9c2) stimulated by isoproterenol as a model to focus on glucose metabolism, oxidative stress, apoptosis, and extracellular signal-regulated protein kinases (ERKs) expression.

RESULTS

In hypertrophied myoblasts, anaerobic glycolysis became prominent at day 7 of isoproterenol stimulation (ISO7; isoproterenol was administered for 7 days). Hydroperoxides production started to increase at day 5 of isoproterenol stimulation (ISO5) and peaked at ISO7. Apoptotic cell death was significantly increased in ISO5 and ISO7. Temporary ERKs suppression was also found at ISO5 and ISO7. Change in glucose metabolism led to stimulation of hydroperoxides production, apoptotic cell death and suppression of ERKs.

CONCLUSION

We concluded that oxidative stress was increased during the progression of hypertrophied myoblasts in association with impaired glucose metabolism and increased apoptotic cell death. Suppression of ERKs may be involved in signal transduction of apoptotic cell death.