Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10739881 | Free Radical Biology and Medicine | 2005 | 13 Pages |
Abstract
The NF-κB/iNOS pathway stimulates muscle differentiation downstream of the PI 3-kinase/p38 MAPK pathway and diverse antioxidants block muscle differentiation. Therefore, we here investigated whether Nox 2 links those two myogenic 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-κB/iNOS pathway during muscle differentiation. Nox 2 activity was also increased during muscle differentiation. Treatment with DPI and apocynin, two inhibitors of NADPH oxidase, and suppression of Nox 2 expression using siRNA, but not Nox 1, inhibited NADPH oxidase activity, muscle differentiation, and the NF-κB/iNOS pathway. Inhibition of PI 3-kinase and p38 MAPK suppressed the Nox 2/NF-κB/iNOS pathway. Nitric oxide restored muscle differentiation blocked by treatment with antioxidants or suppression of the Nox 2/NF-κB/iNOS pathway. In conclusion, Nox 2 stimulates muscle differentiation downstream of the PI 3-kinase/p38 MAPK pathway by activating the NF-κB/iNOS pathway via ROS generation.
Keywords
DPIPMSFDCF-DAiNOSproliferation mediumPDTCdeferoxamine mesylateFBSIGFDMEMNF-κBEMSA2′,7′-dichlorodihydrofluorescein diacetatel-NAMEDulbecco's modified Eagle's mediump38 MAPKPI 3-kinaseSmall interfering RNAROSsiRNAelectrophoretic mobility-shift assaydifferentiation mediumMuscle differentiationFree radicalsMyosin heavy chainfetal bovine seruminducible nitric oxide synthaseInsulin-like growth factornuclear factor-κBPhosphatidylinositol 3-kinaseTironMHCsodium nitroprussideNitric oxidep38 mitogen-activated protein kinaseSNPReactive oxygen species (ROS)Reactive oxygen species
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Authors
Yu Ji Piao, Yong Hak Seo, Feng Hong, Jin Hwan Kim, Young-Joo Kim, Myung Ho Kang, Bum Shik Kim, Sangmee Ahn Jo, Inho Jo, Dae-Myung Jue, Insug Kang, Joohun Ha, Sung Soo Kim,