Journal Article Nrf2 deficiency does not affect denervation‐induced alterations in mitochondrial fission and fusion proteins in skeletal muscle

Kitaoka, Yu  ,  Takeda, Kohei  ,  Tamura, Yuki  ,  Fujimaki, Shin  ,  Takemasa, Tohru  ,  Hatta, Hideo

4 ( 24 )  , p.e13064 , 2016-12 , Wiley
Oxidative stress-induced mitochondrial dysfunction is associated with age-related and disuse-induced skeletal muscle atrophy. However, the role ofnuclear factor erythroid 2-related factor 2 (Nrf2) during muscle fiber atrophyremains to be elucidated. In this study, we examined whether deficiency ofNrf2, a master regulator of antioxidant transcription, promotes denervation-induced mitochondrial fragmentation and muscle atrophy. We found that theexpression of Nrf2 and its target antioxidant genes was upregulated at 2 weeksafter denervation in wild-type (WT) mice. The response of these antioxidantgenes was attenuated in Nrf2 knockout (KO) mice. Nrf2 KO mice exhibitedelevated levels of 4-hydroxynonenal in the skeletal muscle, whereas the proteinlevels of the mitochondrial oxidative phosphorylation complex IV wasdeclined in the denervated muscle of these mice. Increased in mitochondrialfission regulatory proteins and decreased fusion proteins in response to dener-vation were observed in both WT and KO mice; however, no difference wasobserved between the two groups. These findings suggest that Nrf2 deficiencyaggravates denervation-induced oxidative stress, but does not affect the alter-ations in mitochondrial morphology proteins and the loss of skeletal musclemass.

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