Résumé :
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Green tea polyphenols (GTP) and their major compound epigallocatechin gallate (EGCG) are known for a wide range of health-promoting properties, such as antioxidant, anticancer, anti-inflammatory, antibacterial, antiviral, antifibrotic, hypolipidemic, cardioprotective or brain-protective properties. We have previously shown that GTP and EGCG improved muscle structure and function in a mouse model (mdx5Cv) for Duchenne muscular dystrophy (DMD). Chronic elevation of intracellular Ca2+ concentration is one of the typical characteristics in dystrophic muscle. Our earlier results showed that GTP and EGCG modulate cellular Ca2+ handling. Intracellular calcium levels play a role in signaling functions and are modulated by calcium regulating proteins, including the Ca2+-ATPase from sarco/endoplasmic reticulum (SERCA). In this context, we investigated the effects of oral administration (5-16 weeks treatment) of GTP, EGCG, prednisolone (PDN, a drug used in DMD therapy), a combination of EGCG & PDN and pentoxifylline (PTX, as a positive control) on SERCA function in dystrophic mdx5Cv mice.We have found elevation of SERCA activity and expression in mdx5Cv mice skeletal muscle of ages 2 and 8 month (young and adult animals), respectively. Concerning kinetic parameters, maximum reaction velocity increment was observed in mdx5Cv mice indicating an increase in number of active enzyme molecules and structural modification of protein domains of SERCA in mdx5Cv muscle. Also the Ca2+ and ATP affinities of the enzyme were altered. GTP, EGCG and PTX administration normalized the increased SERCA activity in mdx5Cv samples to the control level. EGCG was more potent than GTP. Combination treatment of EGCG & PDN also induced a significant decrease of SERCA activity to the control level. Effects of GTP, EGCG, PDN and PTX were also investigated in vitro on isolated SERCA to examine their potency to acutely modulate the activity of this enzyme. PDN and PTX did not significantly influence the SERCA activity. GTP and EGCG significantly decreased the enzyme activity at high concentrations (100-250 ?M), EGCG being again more potent. Co-workers in the lab (see Poster by Dorchies, Gallo, et al) have found that GTP and EGCG inhibit calcium influx through membrane channels in dystrophic muscle fibers. We believe that the loss of compensatory SERCA activity is a consequence of GTP-mediated prevention of chronic calcium elevation.
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