Nox 2 stimulates muscle differentiation via NF-κB/iNOS pathway

The NF-kappa B/iNOS pathway stimulates muscle differentiation downstream of the PT 3-kinase/p38 MAPK pathway and diverse antioxidants block muscle differentiation. Therefore, we here investigated whether Nox 2 links those two rnyogenic pathways in H9c2 and C2C12 myoblasts. Compared with the proliferation stage, ROS generation was enhanced from the early stage of differentiation and gradually increased as differentiation progressed. Antioxidants suppressed the activated NF-kappa B/iNOS pathway during muscle differentiation. Nox 2 activity was also increased during muscle differentiation. Treatment with DPI and apocynin, two inhibitors of NADPH oxiclase, and suppression of Nox 2 expression using siRNA, but not Nox 1, inhibited NADPH oxidase activity, muscle differentiation, and the NF-kappa B/iNOS pathway. Inhibition of PI 3-kinase and p38 MAPK suppressed the Nox 21NF-kappa B/iNOS pathway. Nitric oxide restored muscle differentiation blocked by treatment with antioxidants or Suppression of the Nox 2tNF-kappa B/iNOS pathway. In conclusion, Nox 2 stimulates muscle differentiation downstream of the PI 3-kinase/p38 MAPK pathway by activating the NF-kappa B/iNOS pathway via ROS generation. (c) 2005 Published by Elsevier Inc.