Development of an in-vitro model system to investigate the mechanism of muscle protein catabolism induced by proteolysis-inducing factor.
Bottom Line: In myoblasts this followed a bell-shaped dose-response curve with maximal effects at a proteolysis-inducing factor concentration between 2 and 4 nM, while in myotubes increased protein degradation was seen at all concentrations of proteolysis-inducing factor up to 10 nM, again with a maximum of 4 nM proteolysis-inducing factor.There was also an increased expression of the 19S regulatory complex as well as the ubiquitin-conjugating enzyme (E2(14k)), and in myotubes a decrease in myosin expression was seen with increasing concentrations of proteolysis-inducing factor.These results show that proteolysis-inducing factor co-ordinately upregulates both ubiquitin conjugation and proteasome activity in both myoblasts and myotubes and may play an important role in the muscle wasting seen in cancer cachexia.
Affiliation: Department of Physiology and Biophysics, University of Campinas, UNICAMP, SP, Brazil 13083-970. M.J.Tisdale@aston.ac.ukShow MeSH
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Mentions: Further studies were carried out using C2C12 myotubes, since these contain the myofibrillar proteins actin and myosin, characteristic of skeletal muscle. The effect of PIF on total protein catabolism, as determined by [3H]phenylalanine release is shown in Figure 4AFigure 4
Affiliation: Department of Physiology and Biophysics, University of Campinas, UNICAMP, SP, Brazil 13083-970. M.J.Tisdale@aston.ac.uk