Proteasome inhibitor MG-132 enhances whole-body protein turnover in rat |
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Authors: | Holecek Milan Muthny Tomas Kovarik Miroslav Sispera Ludek |
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Institution: | Department of Physiology, Charles University, Medical Faculty, Hradec Kralove, Czech Republic. holecek@lfhk.cuni.cz |
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Abstract: | Proteasome inhibitors are novel therapeutic agents which may be used in treatment of cancer and other severe disorders. We studied the effect of proteasome inhibitor MG-132 on protein and amino acid metabolism. In MG-132-treated rats we observed a significant decrease in proteasome-dependent proteolysis in skeletal muscle and an increase in whole-body protein turnover (i.e., increase in whole-body proteolysis and protein synthesis). Proteasome-dependent proteolysis was activated in the liver and kidney, protein synthesis increased in skeletal muscle, liver, and kidney. Insignificant changes were found in jejunum and colon. MG-132 administration induced a significant increase in concentration of several amino acids in blood plasma and their decrease in jejunum and colon. We conclude that administration of MG-132 affects both protein anabolic and protein catabolic pathways via the direct effect on proteasome-dependent proteolysis and indirect effect on proteolysis and protein synthesis via unidentified mediators. |
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Keywords: | Proteasome Inhibitor Protein metabolism Ubiquitin Nutrition Amino acids |
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