Functional alterations in sarcoplasmic reticulum membranes of magnesium-deficient rat skeletal muscle as consequences of free radical-mediated process.
Free radical-induced physiopathologies are generally thought to be mediated by membrane injuries. Using a pro-oxidant model induced by dietary magnesium deficiency, we have recently shown that skeletal muscle lesions occurred with a rise in the calcium level and enhanced free radical production. In this study, we investigated the physicochemical and biochemical properties of sarcoplasmic reticulum membranes isolated from hind limb muscles of weanling male rats pair fed magnesium-deficient or control diets for 12 d. The calcium-induced calcium efflux from preloaded vesicles was increased in membranes isolated from Mg-deficient rat muscle. In agreement with this latter observation, we demonstrated increased ryanodine binding affinity of the calcium channel. The Ca2(+)-ATPase activity of the pump was shown to be reduced. The viscosity state of the membranes, assessed by 1,6-diphenyl-1,3,5-hexatriene fluorescence anisotropy, was significantly increased in Mg-deficient membranes. Moreover, these membranes demonstrated an increased content of protein carbonyls as compared with controls. These functional as well as structural changes are closed to those described in sarcoplasmic reticulum membranes oxidatively modified in vitro. Together, these data fitted well with the concept that free radical-induced membrane damages resulting in calcium overload may be at the origin of skeletal muscle lesion during Mg-deficiency.
Astier
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Institut National de la Recherche Agronomique, Laboratoire des Maladies Métaboliques, C.R.N.H. de Clermont-Ferrand/Theix, St-Genès-Champanelle, France.
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Gueux
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Mazur
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Rayssiguier
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D000818:Animals; D015220:Calcium Channels / Q000187:drug effects; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D005454:Fluorescence Polarization; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008274:Magnesium / Q000008:administration & dosage / Q000097:blood; D008275:Magnesium Deficiency / Q000378:metabolism*; D008297:Male; D008560:Membrane Fluidity; D018482:Muscle, Skeletal / Q000378:metabolism*; D010084:Oxidation-Reduction; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*
D015220:Calcium Channels; D012433:Ryanodine; D000252:Calcium-Transporting ATPases; D008274:Magnesium