Japan Society for the Promotion of Science:Grants-in-Aid for Scientific Research
Date (from‐to) : 2018/04 -2022/03
Author : Okutsu Mitsuharu
Antioxidants reduce oxidative stress and protect muscle from atrophy. However, a functional role and molecular mechanism regulating the production antioxidants remains to be determined. Here, we demonstrated that Lewis lung carcinoma (LLC) cells implantation in mice induced severe muscle atrophy, as well as atrogenes and oxidative marker in associated with poor antioxidants expression. LLC implantation increased superoxide dismutase (SOD) protein expression in association with Nrf2 activation. Muscle-specific Nrf2 knockout (Nrf2mKO) mice induced severe cachexia-induced muscle atrophy in associated with blunted cachexia-induced SOD expression. Muscle-specific p62 overexpression (p62mTg) mice increased phosphorylated p62, Nrf2 activity, and SOD expression. Importantly, p62mTg mice protected cancer cachexia-induced muscle atrophy. Collectively, these findings indicate that Nrf2 activation by p62 plays an important role for the protection of cachexia-induced muscle atrophy.