""The rate-limiting step of cholesterol biosynthetic. pathway is catalyzed by 3-hydroxy-3-methylglutaryl. coenzyme reductase (HGMR), whose inhibitors,. the statins, widely used in clinical practice to treat. hypercholesterolemia, often cause myopathy, and. rarely rhabdomyolysis. All studies to date are limited to. the definition of statin-induced myotoxicity omitting to. investigate whether and how HMGR inhibition influences. muscle functions. To this end, 3-mo-old male rats. (Rattus norvegicus) were treated for 3 wk with a daily. intraperitoneal injection of simvastatin (1.5 mg\\\/kg\\\/d),. and biochemical, morphological, mechanical, and functional. analysis were performed on extensor digitorum. longus (EDL) muscle. Our results show that EDL. muscles from simvastatin-treated rats exhibited reduced. HMGR activity; a 15% shift from the fastest. myosin heavy-chain (MHC) isoform IIb to the slower. IIa\\\/x; and reduced power output and unloaded shortening. velocity, by 41 and 23%, respectively, without any. change in isometric force and endurance. Moreover,. simvastatin-treated rats showed a decrease of maximum. speed reached and the latency to fall off the rotaroad. (30%). These results indicate that the molecular. mechanism of the impaired muscle function following. statin treatment could be related to the plasticity of fast. MHC isoform expression.—Trapani, L., Melli, L., Segatto,. M., Trezza, V., Campolongo, P., Jozwiak, A.,. Swiezewska, E., Pucillo, L.P., Moreno, S., Fanelli, F.,. Linari, M., Pallottini, V. Effects of myosin heavy chain. (MHC) plasticity induced by HMGCoA-reductase inhibition. on skeletal muscle functions.""

TRAPANI L, MELLI L, SEGATTO M, TREZZA V, CAMPOLONGO P, JOZWIAK A, et al. (2011). Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions. THE FASEB JOURNAL, 25(11), 4037-4047 [10.1096/fj.11-184218].

Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions

SEGATTO, MARCO;TREZZA, VIVIANA;MORENO, Sandra;PALLOTTINI, Valentina
2011

Abstract

""The rate-limiting step of cholesterol biosynthetic. pathway is catalyzed by 3-hydroxy-3-methylglutaryl. coenzyme reductase (HGMR), whose inhibitors,. the statins, widely used in clinical practice to treat. hypercholesterolemia, often cause myopathy, and. rarely rhabdomyolysis. All studies to date are limited to. the definition of statin-induced myotoxicity omitting to. investigate whether and how HMGR inhibition influences. muscle functions. To this end, 3-mo-old male rats. (Rattus norvegicus) were treated for 3 wk with a daily. intraperitoneal injection of simvastatin (1.5 mg\\\/kg\\\/d),. and biochemical, morphological, mechanical, and functional. analysis were performed on extensor digitorum. longus (EDL) muscle. Our results show that EDL. muscles from simvastatin-treated rats exhibited reduced. HMGR activity; a 15% shift from the fastest. myosin heavy-chain (MHC) isoform IIb to the slower. IIa\\\/x; and reduced power output and unloaded shortening. velocity, by 41 and 23%, respectively, without any. change in isometric force and endurance. Moreover,. simvastatin-treated rats showed a decrease of maximum. speed reached and the latency to fall off the rotaroad. (30%). These results indicate that the molecular. mechanism of the impaired muscle function following. statin treatment could be related to the plasticity of fast. MHC isoform expression.—Trapani, L., Melli, L., Segatto,. M., Trezza, V., Campolongo, P., Jozwiak, A.,. Swiezewska, E., Pucillo, L.P., Moreno, S., Fanelli, F.,. Linari, M., Pallottini, V. Effects of myosin heavy chain. (MHC) plasticity induced by HMGCoA-reductase inhibition. on skeletal muscle functions.""
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11590/278981
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