Downregulation of ubiquitin-dependent protein degradation in murine myotubes during hyperthermia by eicosapentaenoic acid.
Muscle atrophy in a number of acute wasting conditions is associated with an increased activity and expression of the ubiquitin-proteasome proteolytic pathway. Although different initiators are involved, it is possible that the intracellular signalling events leading to upregulation of this pathway are the same in all catabolic conditions. This study investigates hyperthermia in murine myotubes as a model for increased protein degradation through the ubiquitin-proteasome pathway. The effect of eicosapentaenoic acid (EPA) on this process should identify common elements, since EPA has been shown to attenuate induction of the ubiquitin-proteasome pathway in cancer cachexia. Increasing the temperature of myotubes caused a progressive increase in protein degradation. This was associated with an increased proteasome 'chymotrypsin-like' enzyme activity, as well as increased expression of both mRNA and protein for 20S proteasome subunits and the ubiquitin-conjugating enzyme (E2(14k)). This upregulation was not seen in cultures treated with EPA (50 microM), suggesting that it acts to prevent transcriptional activation of the ubiquitin-proteasome pathway in hyperthermia. These results suggest that protein catabolism in hyperthermia and cancer cachexia is mediated through a common pathway.
Smith
Helen J
HJ
Molecular Biosciences, School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK.
Khal
Jwan
J
Tisdale
Michael J
MJ
D000818:Animals; D001673:Biodegradation, Environmental / Q000187:drug effects; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005334:Fever / Q000378:metabolism*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D013696:Temperature; D015533:Transcriptional Activation / Q000187:drug effects*; D025801:Ubiquitin / Q000378:metabolism*
D025801:Ubiquitin; D015118:Eicosapentaenoic Acid; D046988:Proteasome Endopeptidase Complex