A proinflammatory tumor that activates protein degradation sensitizes rats to catabolic effects of endotoxin

1 Department of Agricultural, Food, and Nutritional Science; 2 Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; and 3 Polypeptide Laboratory, Department of Medicine, McGill University, Montreal, Quebec, Canada Submitted 4 February 2005 ; accepted in final form 27 May 2005 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 µg/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 =