Induction of protein catabolism and the ubiquitin-proteasome pathway by mild oxidative stress.
Muscle wasting in cancer cachexia is associated with increased levels of malondialdehyde (MDA) in gastrocnemius muscles, suggesting an increased oxidative stress. To determine whether oxidative stress contributes to muscle protein catabolism, an in vitro model system, consisting of C2C12 myotubes, was treated with either 0.2 mM FeSO4, 0.1 mM H2O2, or both, to replicate the rise in MDA content in cachexia. All treatments caused an increased protein catabolism and a decreased myosin expression. There was an increase in the proteasome chymotrypsin-like enzyme activity, while immunoblotting showed an increased expression of the 20S proteasome alpha-subunits, p42, and the ubiquitin-conjugating enzyme, E214k. These results show that mild oxidative stress increases protein degradation in skeletal muscle by causing an increased expression of the major components of the ubiquitin-proteasome pathway.
Gomes-Marcondes
Maria Cristina C
MC
Department of Physiology and Biophysics, University of Campinas, UNICAMP, SP Brazil.
Tisdale
Michael J
MJ
D000818:Animals; D015153:Blotting, Western; D002100:Cachexia / Q000378:metabolism*; D002478:Cells, Cultured; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004527:Egg Proteins / Q000378:metabolism; D008315:Malondialdehyde / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology; D009218:Myosins / Q000378:metabolism; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface; D013997:Time Factors; D025801:Ubiquitin / Q000378:metabolism*; D000072216:Zona Pellucida Glycoproteins
D004527:Egg Proteins; D008562:Membrane Glycoproteins; D009097:Multienzyme Complexes; D011506:Proteins; D011956:Receptors, Cell Surface; D025801:Ubiquitin; D000072216:Zona Pellucida Glycoproteins; D008315:Malondialdehyde; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D009218:Myosins