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This Article Full Text Full Text (PDF) All Versions of this Article: 289/4/E527    most recent 00050.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Mackenzie, M. L. Articles by Baracos, V. E. Search for Related Content PubMed PubMed Citation Articles by Mackenzie, M. L. Articles by Baracos, V. E.

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

¹Department of Agricultural, Food, and Nutritional Science; ²Department of Oncology, University of Alberta, Edmonton, Alberta, Canada; and ³Polypeptide 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 = <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.

muscle wasting; inflammation; ubiquitin proteolytic pathway