Up-regulation of calcium-dependent proteolysis in human myoblasts under acute oxidative stress.
The reduced regenerative potential of muscle fibres, most likely due to a decreased number and/or function of satellite cells, could play a significant role in the progression of muscle ageing. Accumulation of reactive oxygen species has been clearly correlated to sarcopenia and could contribute to the impairment of satellite cell function. In this work we have investigated the effect of oxidative stress generated by hydrogen peroxide in cultured human skeletal muscle satellite cells. We specifically focused on the activity and regulation of calpains. These calcium-dependent proteases are known to regulate many transduction pathways including apoptosis and play a critical role in satellite cell function. In our experimental conditions, which induce an increase in calcium concentration, protein oxidation and apoptotic cell death, a significant up-regulation of calpain expression and activity were observed and ATP synthase, a major component of the respiratory chain, was identified as a calpain target. Interestingly we were able to protect the cells from these H(2)O(2)-induced effects and prevent calpain up-regulation with a natural antioxidant extracted from pine bark (Oligopin). These data strongly suggest that oxidative stress could impair satellite cell functionality via calpain-dependent pathways and that an antioxidant such as Oligopin could prevent apoptosis and calpain activation.
Dargelos
Elise
E
Université Bordeaux 1, Unité Protéolyse Croissance et Développement Musculaire, INRA, USC 2009, Avenue des Facultés, F-33405 Talence, France. elise.dargelos@enscpb.fr
Brulé
Cédric
C
Stuelsatz
Pascal
P
Mouly
Vincent
V
Veschambre
Philippe
P
Cottin
Patrick
P
Poussard
Sylvie
S
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002154:Calpain / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D022083:Cytoplasmic Structures / Q000378:metabolism; D004151:Dipeptides / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010636:Phenols / Q000494:pharmacology; D028223:Pinus / Q000737:chemistry; D010936:Plant Extracts / Q000494:pharmacology; D059808:Polyphenols; D050050:Protein Carbonylation / Q000187:drug effects; D032496:Satellite Cells, Skeletal Muscle / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000975:Antioxidants; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D005419:Flavonoids; D010636:Phenols; D010936:Plant Extracts; D059808:Polyphenols; C071482:calpeptin; D006861:Hydrogen Peroxide; D048051:p38 Mitogen-Activated Protein Kinases; D002154:Calpain; C449000:m-calpain; C449002:mu-calpain; D025261:Mitochondrial Proton-Translocating ATPases