3-hydroxy 3-methylglutaryl coenzyme A reductase increase is essential for rat muscle differentiation.
3-Hydroxy 3-methylglutaryl coenzyme A reductase (HMG-CoAR) is the key and rate-limiting enzyme of cholesterol biosynthetic pathway. Although HMG-CoAR activity has already been related to the differentiation of some cellular lines there are no studies that analyze the role of HMG-CoAR, and the pathway it is involved with in a fully characterized muscle differentiation model. Thus, the aim of this work is to evaluate such role and delineate the pathway involved in foetal rat myoblasts (L6) induced to differentiate by insulin -- a standard and feasible model of the myogenic process. The results obtained by biochemical and morphological approaches demonstrate that (i) HMG-CoAR increase is crucial for differentiation induction, (ii) p21waf, whose increase is a necessary requisite for differentiation to occur, rises downstream HMG-CoAR activation, (iii) the main role of p38/MAPK as key regulator also for HMG-CoAR. Pathologies characterized by muscle degeneration might benefit from therapeutic programmes committed to muscle function restoration, such as modulation and planning myoblast differentiation. Thus, the important role of HMG-CoAR in muscular differentiation providing new molecular basis for the control of muscle development can help in the design of therapeutic treatment for diseases characterized by the weakening of muscular fibers and aging-related disorders (sarcopenia).
Martini
Chiara
C
Department of Biology, University of Roma Tre, Rome, Italy.
Trapani
Laura
L
Narciso
Laura
L
Marino
Maria
M
Trentalance
Anna
A
Pallottini
Valentina
V
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008148:Lovastatin / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology* / Q000502:physiology*; D051381:Rats; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D050759:Cyclin-Dependent Kinase Inhibitor p21; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007328:Insulin; D002784:Cholesterol; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D048051:p38 Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein