Skeletal muscle has the ability to regenerate new muscle fibers after injury. The process of new muscle formation requires that quiescent mononuclear muscle precursor cells (myoblasts) become activated, proliferate, differentiate, and fuse into multinucleated myotubes which, in turn, undergo further differentiation and mature to form functional muscle fibers. Previous data demonstrated the crucial role played by 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR), the rate-limiting enzyme of cholesterol biosynthetic pathway, in fetal rat myoblast (L6) differentiation. This finding, along with epidemiological studies assessing the myotoxic effect of statins, HMGR inhibitors, allowed us to speculate that HMGR could be strongly involved in skeletal muscle repair. Thus, our research was aimed at evaluating such involvement: in vitro and in vivo experiments were performed on both mouse adult satellite cell derived myoblasts (SCDM) and mouse muscles injured with cardiotoxin. Results demonstrate that HMGR inhibition by the statin Simvastatin reduces SCDM fusion index, fast MHC protein levels by 60% and slow MHC by 40%. Most importantly, HMGR inhibition delays skeletal muscle regeneration in vivo. Thus, besides complaining of myopathies, patients given Simvastatin could also undergo an impairment in muscle repair.

3-hydroxy 3-methylglutaryl coenzyme a reductase inhibition impairs muscle regeneration / Trapani, Laura; Segatto, Marco; La Rosa, Piergiorgio; Fanelli, Francesca; Moreno, Sandra; Marino, Maria; Pallottini, Valentina. - In: JOURNAL OF CELLULAR BIOCHEMISTRY. - ISSN 0730-2312. - ELETTRONICO. - 113:6(2012), pp. 2057-2063. [10.1002/jcb.24077]

3-hydroxy 3-methylglutaryl coenzyme a reductase inhibition impairs muscle regeneration

SEGATTO, MARCO;La Rosa, Piergiorgio;
2012

Abstract

Skeletal muscle has the ability to regenerate new muscle fibers after injury. The process of new muscle formation requires that quiescent mononuclear muscle precursor cells (myoblasts) become activated, proliferate, differentiate, and fuse into multinucleated myotubes which, in turn, undergo further differentiation and mature to form functional muscle fibers. Previous data demonstrated the crucial role played by 3-hydroxy 3-methylglutaryl coenzyme A reductase (HMGR), the rate-limiting enzyme of cholesterol biosynthetic pathway, in fetal rat myoblast (L6) differentiation. This finding, along with epidemiological studies assessing the myotoxic effect of statins, HMGR inhibitors, allowed us to speculate that HMGR could be strongly involved in skeletal muscle repair. Thus, our research was aimed at evaluating such involvement: in vitro and in vivo experiments were performed on both mouse adult satellite cell derived myoblasts (SCDM) and mouse muscles injured with cardiotoxin. Results demonstrate that HMGR inhibition by the statin Simvastatin reduces SCDM fusion index, fast MHC protein levels by 60% and slow MHC by 40%. Most importantly, HMGR inhibition delays skeletal muscle regeneration in vivo. Thus, besides complaining of myopathies, patients given Simvastatin could also undergo an impairment in muscle repair.
2012
HMG-CoA REDUCTASE; MUSCLE REGENERATION; MYOSIN HEAVY CHAIN; SATELLITE CELLS; STATINS; Animals; Cardiotoxins; Cell Differentiation; Female; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Mevalonic Acid; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal; Muscle, Skeletal; Myoblasts; Regeneration; Simvastatin; Biochemistry; Cell Biology; Molecular Biology
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3-hydroxy 3-methylglutaryl coenzyme a reductase inhibition impairs muscle regeneration / Trapani, Laura; Segatto, Marco; La Rosa, Piergiorgio; Fanelli, Francesca; Moreno, Sandra; Marino, Maria; Pallottini, Valentina. - In: JOURNAL OF CELLULAR BIOCHEMISTRY. - ISSN 0730-2312. - ELETTRONICO. - 113:6(2012), pp. 2057-2063. [10.1002/jcb.24077]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/974141
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