TNF-alpha-mediated reduction in PGC-1alpha may impair skeletal muscle function after cigarette smoke exposure.

ABSTRACT: Skeletal muscle dysfunction contributes to exercise limitation in COPD. In this study cigarette smoke exposure was hypothesized to increase expression of the inflammatory cytokine, TNF-alpha, thereby suppressing PGC-1alpha, and hence affecting down stream molecules that regulate oxygen transport and muscle function. Furthermore, we hypothesized that highly vascularized oxidative skeletal muscle would be more susceptible to cigarette smoke than less well-vascularized glycolytic muscle. To test these hypotheses, mice were exposed to cigarette smoke daily for 8 or 16 weeks, resulting in 157% (8 weeks) and 174% (16 weeks) increases in serum TNF-alpha. Separately, TNF-alpha administered to C2C12 myoblasts was found to dose-dependently reduce PGC-1alpha mRNA. In the smoke-exposed mice, PGC-1alph

SUBMITTER: Tang K 

PROVIDER: S-EPMC5831677 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature