Downregulation of muscle protein degradation in sepsis by eicosapentaenoic acid (EPA).
Eicosapentaenoic acid (EPA) has been shown to attenuate muscle atrophy in cancer, starvation and hyperthermia by downregulating the increased expression of the ubiquitin-proteasome proteolytic pathway leading to a reduction in protein degradation. In the current study EPA (0.5 g/kg) administered to septic mice completely attenuated the increased protein degradation in skeletal muscle by preventing the increase in both gene expression and protein concentration of the alpha- and beta-subunits of the 20S proteasome, as well as functional activity of the proteasome, as measured by the 'chymotrypsin-like' enzyme activity. These results suggest that muscle protein catabolism in sepsis is mediated by the same intracellular signalling pathways as found in other catabolic conditions.
Khal
Jwan
J
Nutritional Biomedicine, School of Life and Health Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UK.
Tisdale
Michael J
MJ
D000818:Animals; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism / Q000382:microbiology; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D018805:Sepsis / Q000150:complications / Q000378:metabolism*; D013211:Staphylococcus aureus
D009124:Muscle Proteins; D012333:RNA, Messenger; D015118:Eicosapentaenoic Acid; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; C096184:proteasome component C5