Prolonged immobilization (IM) results in skeletal muscle atrophy accompanied by increased reactive oxygen species (ROS), inflammation, and protein degradation. In this study, we examined peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) controlled mitochondrial biogenesis pathway and inflammatory response in mice subjected to two weeks of hindlimb IM followed by five days of remobilization (RM). FVB/N mice (age 2 mo) were randomly assigned to either 14 days of IM with capping one of the hindlimbs (N=7), IM followed by 5 day of RM with cap removed (N=7), or control (Con, N=7). Protein contents of PGC-1α and nuclear respiratory factor (NRF)-1 and -2 in tibialis anterior (TA) muscle was reduced by 50% (p<0.01) in IM vs. Con, with no recovery seen during RM. IM suppressed mitochondrial transcription factor A and cytochrome c content by 57% and 63% (P<0.01), respectively and cytochrome c oxidase activity by 58% (P<0.05). Furthermore, mitochondrial DNA content was reduced by 71% (P<0.01) with IM. None of these changes was reversed after RM. With RM, TA muscle showed a 2.3-fold (P<0.05) and 4-fold (P<0.01) higher H2O2 and 8-isoprostane contents, respectively, compared with Con, indicating an oxidative stress. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels in TA muscle were 4- and 3-fold higher (P<0.05), respectively, in IM or RM vs. CON, NFκB pathway activation was observed only after RM, but not after IM alone. These data indicate that during the initial phase of muscle RM there is an increase in ROS generation that could activate NFkB pathway and elicit inflammation and oxidative stress.
- Copyright © 2012, Journal of Applied Physiology