PROTEIN-TURNOVER IN SKELETAL-MUSCLE OF TUMOR-BEARING TRANSGENIC MICE OVEREXPRESSING THE SOLUBLE TNF RECEPTOR-1

The implantation of the Lewis lung carcinoma (a fast-growing mouse tum our that induces cachexia) to both wild-type and transgenic mice for t he soluble TNF receptor type I protein (sTNF-R1) resulted in a conside rable loss of carcass weight in both groups. However, while in the wil d-type mice there was a loss of both fat and muscle, in the transgenic mice muscle waste was not affected to the same extent as in the wild- type group. Muscle waste in wild-type mice was accompanied by an incre ase in the fractional rate of protein degradation, while no changes we re observed in protein synthesis. The result was a decreased rate of p rotein accumulation which accounted for the muscle weight loss observe d as a result of the tumour burden. In contrast, transgenic mice did n ot have such low rates of protein accumulation after tumour implantati on. The increase in protein degradation in the tumour-bearing transgen ic mice was accompanied by a similar increase in protein synthesis whi ch compensated for the loss of muscle protein by degradation. Both tum our-bearing groups showed an enhanced expression of ubiquitin and prot easome C8 subunit genes, all of them related to the activation of the ATP-dependent proteolytic system in skeletal muscle. It is suggested t hat TNF may, in part, be responsible for the loss of protein in skelet al muscle of tumour-bearing mice. 1998 Published by Elsevier Science I reland Ltd. All rights reserved.