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Publication : Weight gain does not preclude increased ubiquitin conjugation in skeletal muscle: an exploratory study in tumor-bearing mice.

First Author  Jatoi A Year  2001
Journal  Ann Nutr Metab Volume  45
Issue  3 Pages  116-20
PubMed ID  11423703 Mgi Jnum  J:70639
Mgi Id  MGI:2137929 Doi  10.1159/000046716
Citation  Jatoi A, et al. (2001) Weight gain does not preclude increased ubiquitin conjugation in skeletal muscle: an exploratory study in tumor-bearing mice. Ann Nutr Metab 45(3):116-20
abstractText  Background and Hypothesis: At least 13 studies have shown that the ubiquitin-proteasome system mediates muscle wasting in weight-losing cancer subjects. We hypothesized that cancer itself may activate the ubiquitin-proteasome system, regardless of weight loss. Methods: We utilized hybrid mice obtained by crossing Mouse Mammary Tumor Virus-Transforming Growth Factor-alpha (TGF-alpha) mice with the Lep(ob) strain. Five hybrid MMTV-TGF-alpha heterozygous Lep(+)Lep(ob) female mice with mammary tumors were used; 4 nontransgenic heterozygous Lep(+)Lep(ob) female mice served as controls. Ubiquitin conjugates were quantitated from hamstring and paraspinal muscles by Western blotting. Myocyte apoptosis was determined by a modified TUNEL assay. Results: All mice gained weight, even after tumor development. Higher concentrations of muscle ubiquitin conjugates were seen in the 5 tumor-bearing, TGF-alpha transgenic mice as compared with the 4 non-tumor-bearing mice: median (range) in arbitrary densitometric units: 0.67 (0.22-4.59) versus 0.18 (0.08-0.44) in hamstring muscle and 0.56 (0.23-20.15) versus 0.18 (0.08-0.25) in paraspinal muscle (p = 0.04 and p = 0.04, respectively; Mann-Whitney U test). Apoptosis was not seen in any muscle sample studied. Conclusions: Ubiquitin conjugates are increased in the skeletal muscle of tumor-bearing mice in the absence of weight loss. Such activation is not seen in the skeletal muscle on non-tumor-bearing mice. Further studies might focus of whether this observation is relevant to cancer-associated wasting of lean tissue. Copyright 2001 S. Karger AG, Basel
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