Nox2 Inhibition Regulates Stress Response and Mitigates Skeletal Muscle Fiber Atrophy during Simulated Microgravity

Insufficient stress response and elevated oxidative can contribute to skeletal muscle atrophy during mechanical unloading (e.g., spaceflight bedrest). Perturbations in heat shock proteins HSP70), antioxidant enzymes, sarcolemmal neuronal nitric oxidase synthase (nNOS) have been linked unloading-induced atrophy. We recently discovered that the NADPH oxidase-2 complex (Nox2) is unloading, downstream of angiotensin II receptor 1, concomitant with Here, we hypothesized peptidyl inhibition Nox2 would attenuate disruption HSP70, MnSOD, nNOS thus fiber F344 rats were divided into control (CON), hindlimb unloaded (HU), +7.5 mg/kg/day gp91ds-tat (HUG) groups. Unloading-induced elevation subunit p67phox-positive staining was mitigated by gp91ds-tat. HSP70 protein abundance significantly lower HU muscles, but not HUG. MnSOD decreased unloading; however, rescued In contrast, protected against suppression transcription factor Nrf2. bioactivity reduced HU, an effect abrogated inhibition. soleus attenuated These data establish a causal role for atrophy, preservation Nrf2, nNOS.