Inhibition of FoxO transcriptional activity prevents muscle fiber atrophy during cachexia and induces hypertrophy.

ABSTRACT: Cachexia is characterized by inexorable muscle wasting that significantly affects patient prognosis and increases mortality. Therefore, understanding the molecular basis of this muscle wasting is of significant importance. Recent work showed that components of the forkhead box O (FoxO) pathway are increased in skeletal muscle during cachexia. In the current study, we tested the physiological significance of FoxO activation in the progression of muscle atrophy associated with cachexia. FoxO-DNA binding dependent transcription was blocked in the muscles of mice through injection of a dominant negative (DN) FoxO expression plasmid prior to inoculation with Lewis lung carcinoma cells or the induction of sepsis. Expression of DN FoxO inhibited the increased mRNA levels of atrogin-1, MuRF1, cath

SUBMITTER: Reed SA 

PROVIDER: S-EPMC3289501 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature