| First Author | Llovera M | Year | 1998 |
| Journal | Mol Cell Endocrinol | Volume | 142 |
| Issue | 1-2 | Pages | 183-9 |
| PubMed ID | 9783914 | Mgi Jnum | J:50298 |
| Mgi Id | MGI:1298151 | Doi | 10.1016/s0303-7207(98)00105-1 |
| Citation | Llovera M, et al. (1998) Role of TNF receptor 1 in protein turnover during cancer cachexia using gene knockout mice. Mol Cell Endocrinol 142(1-2):183-9 |
| abstractText | The implantation of the Lewis lung carcinoma (a fast-growing mouse tumour that induces cachexia) to both wild-type and gene-deficient mice for the TNF-alpha receptor type I protein (Tnfr1 degree/Tnfr1 degree), resulted in a considerable loss of carcass weight in both groups. However, while in the wild-type mice there was a loss of both fat and muscle, in the gene-knockout mice muscle wastage was not affected to the same extent. In both groups, tumour burden resulted in significant increases in circulating TNF-alpha, a cytokine which, as we have previously demonstrated, can induce protein breakdown in skeletal muscle. Muscle wastage in wild-type mice was accompanied by an increase in the fractional rate of protein degradation, while no changes were observed in protein synthesis. The result is a decreased rate of protein accumulation that accounts for the muscle weight loss observed as a result of tumour burden. In contrast, gene knockout mice did not have significantly lower rates of protein accumulation as a result of tumour implantation. The increase in protein degradation in the tumour-bearing wild mice was accompanied by an enhanced expression of both ubiquitin and proteasome subunit genes, all of them related to the activation of the ATP-dependent proteolytic system in skeletal muscle. Tumour-bearing gene-deficient mice did not show any increase in gene expression. It is concluded that TNF-alpha (alone or in combination with other cytokines) is responsible for the activation of protein breakdown in skeletal muscle of tumour-bearing mice. |
