Object's details: Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions.

Provider:Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

Description

Title:
Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions.
Creator:
Trapani, Laura;
Melli, Luca;
Segatto, Marco;
Trezza, Viviana;
Campolongo, Patrizia;
Jóźwiak, Adam;
Swiezewska, Ewa;
Pucillo, Leopoldo Paolo;
Moreno, Sandra;
Fanelli, Francesca;
Linari, Marco;
Pallottini, Valentina
Description:
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.
Object availability:
free access
Date:
2011.11
Type:
Article;
PeerReviewed
Language:
English
Format:
application/pdf
Relation: http://eprints.ibb.waw.pl/309
Subject:
R Medicine (General);
RB Pathology;
RM Therapeutics. Pharmacology
Identifier: http://eprints.ibb.waw.pl/309/1/4037.pdf ;
Trapani, Laura and Melli, Luca and Segatto, Marco and Trezza, Viviana and Campolongo, Patrizia and Jóźwiak, Adam and Swiezewska, Ewa and Pucillo, Leopoldo Paolo and Moreno, Sandra and Fanelli, Francesca and Linari, Marco and Pallottini, Valentina (2011) Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions. FASEB Journal, 25 (11). pp. 4037-4047. ISSN 1530-6860
Data provider:
Repozytorium Instytutu Biochemii i Biofizyki Polskiej Akademii Nauk

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Object's details: Effects of myosin heavy chain (MHC) plasticity induced by HMGCoA-reductase inhibition on skeletal muscle functions.

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