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Type: Artigo de periódico
Title: Development Of An In-vitro Model System To Investigate The Mechanism Of Muscle Protein Catabolism Induced By Proteolysis-inducing Factor.
Author: Gomes-Marcondes, M C C
Smith, H J
Cooper, J C
Tisdale, M J
Abstract: The mechanism of muscle protein catabolism induced by proteolysis-inducing factor, produced by cachexia-inducing murine and human tumours has been studied in vitro using C(2)C(12) myoblasts and myotubes. In both myoblasts and myotubes protein degradation was enhanced by proteolysis-inducing factor after 24 h incubation. 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. Protein degradation induced by proteolysis-inducing factor was completely attenuated in the presence of cycloheximide (1 microM), suggesting a requirement for new protein synthesis. In both myoblasts and myotubes protein degradation was accompanied by an increased expression of the alpha-type subunits of the 20S proteasome as well as functional activity of the proteasome, as determined by the 'chymotrypsin-like' enzyme activity. 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.
Subject: Adenosine Triphosphatases
Antibodies, Monoclonal
Blood Proteins
Cells, Cultured
Cysteine Endopeptidases
Dose-response Relationship, Drug
Gene Expression Regulation
Macromolecular Substances
Multienzyme Complexes
Muscle Proteins
Muscle, Skeletal
Myosin Heavy Chains
Proteasome Endopeptidase Complex
Protein Subunits
Citation: British Journal Of Cancer. v. 86, n. 10, p. 1628-33, 2002-May.
Rights: fechado
Identifier DOI: 10.1038/sj.bjc.6600236
Date Issue: 2002
Appears in Collections:Unicamp - Artigos e Outros Documentos

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