A proinflammatory tumor that activates protein degradation sensitizes rats to catabolic effects of endotoxin.
Chronic or acute inflammation may participate in the etiology of cancer cachexia. To investigate the interaction between tumor and a secondary inflammatory stimulus on muscle wasting, rats with and without tumors (Yoshida ascites hepatoma) received low doses of endotoxin (LPS, 400 microg/kg sc) or saline. Nitrogen balance was measured 24 h before and after LPS/saline. Epitrochlearis muscle was used to measure in vitro protein metabolism, and gastrocnemius muscle was used for quantification of the mRNA for components of the ubiquitin proteolytic pathway. The YAH reduced muscle mass (P = 0.002), increased muscle protein degradation (P = 0.042), and elevated mRNA expression of components of the ubiquitin proteolytic pathway (P < 0.01) including ubiquitin, ubiquitin-conjugating enzyme E2(14k), and ubiquitin ligases muscle RING Finger 1 and atrogin-1. Although the selected low dose of LPS had no impact on protein metabolism in control rats, LPS in rats bearing YAH caused weight loss (P = 0.0007), lowered nitrogen balance (P = <0.0001), and increased muscle protein degradation (P = 0.0336). In conclusion, the presence of a tumor can potentiate whole body and muscle-specific catabolic losses of protein in response to a stimulus that is not catabolic in healthy animals. This effect might be dependent on the inflammatory nature of the tumor.
Mackenzie
Michelle L
ML
Dept. of Agriculture, Food, and Nutritional Science, University of Alberta, Edmonton, AB, Canada T6G 1Z2.
Bedard
Nathalie
N
Wing
Simon S
SS
Baracos
Vickie E
VE
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology*; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology*; D004305:Dose-Response Relationship, Drug; D008070:Lipopolysaccharides / Q000008:administration & dosage*; D008297:Male; D009124:Muscle Proteins / Q000276:immunology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D009363:Neoplasm Proteins / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D008070:Lipopolysaccharides; D009124:Muscle Proteins; D009363:Neoplasm Proteins