Curcumin counteracts loss of force and atrophy of hindlimb unloaded rat soleus by hampering neuronal nitric oxide synthase untethering from sarcolemma.

作者: Maurizio Vitadello , Elena Germinario , Barbara Ravara , Luciano Dalla Libera , Daniela Danieli-Betto

DOI: 10.1113/JPHYSIOL.2013.268672

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摘要: Antioxidant administration aimed to antagonize the development and progression of disuse muscle atrophy provided controversial results. Here we investigated effects curcumin, a vegetal polyphenol with pleiotropic biological activity, because its ability upregulate glucose-regulated protein 94 kDa (Grp94) expression in myogenic cells. Grp94 is sarco-endoplasmic reticulum chaperone, levels which decrease significantly unloaded muscle. Rats were injected intraperitoneally curcumin soleus was analysed after 7 days hindlimb unloading or standard caging. Curcumin increased about twofold muscles ambulatory rats (P < 0.05) antagonized ones. Treatment countered loss mass myofibre cross-sectional area by approximately 30% ≤ 0.02) maintained force-frequency relationship closer levels. Indexes lipid oxidation, such as carbonylation, revealed Oxyblot, malondialdehyde, measured HPLC, blunted treated compared untreated ones = 0.01). Mechanistic involvement suggested disruption curcumin-induced attenuation transfection antisense grp94 cDNA drug-positive effect on maintenance subsarcolemmal localization active neuronal nitric oxide synthase molecules, displaced sarcoplasm unloading. The absence additive combined inhibitor further supported interference this pro-atrophic pathway. In conclusion, represents an effective safe tool maintain function during unweighting.

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