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Tytuł pozycji:

C2C12 myoblasts are more sensitive to the toxic effects of simvastatin than myotubes and show impaired proliferation and myotube formation.

Tytuł :
C2C12 myoblasts are more sensitive to the toxic effects of simvastatin than myotubes and show impaired proliferation and myotube formation.
Autorzy :
Sanvee GM; Division of Clinical Pharmacology & Toxicology, University Hospital, Basel, Switzerland; Department of Biomedicine, University of Basel, Switzerland. Electronic address: .
Bouitbir J; Division of Clinical Pharmacology & Toxicology, University Hospital, Basel, Switzerland; Department of Biomedicine, University of Basel, Switzerland; Swiss Centre for Applied Human Research (SCAHT), Switzerland. Electronic address: .
Krähenbühl S; Division of Clinical Pharmacology & Toxicology, University Hospital, Basel, Switzerland; Department of Biomedicine, University of Basel, Switzerland; Swiss Centre for Applied Human Research (SCAHT), Switzerland. Electronic address: .
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Źródło :
Biochemical pharmacology [Biochem Pharmacol] 2021 Aug; Vol. 190, pp. 114649. Date of Electronic Publication: 2021 Jun 07.
Typ publikacji :
Journal Article
Język :
English
Imprint Name(s) :
Publication: Oxford : Elsevier Science
Original Publication: Oxford, New York [etc.] Paragamon Press.
Contributed Indexing :
Keywords: C2C12 myoblast proliferation; Insulin signaling; Mevalonate; Muscle regeneration; Myotoxicity; Simvastatin
Entry Date(s) :
Date Created: 20210610 Latest Revision: 20210724
Update Code :
20210724
DOI :
10.1016/j.bcp.2021.114649
PMID :
34111424
Czasopismo naukowe
Statins reduce cardiovascular complications in patients with high LDL-cholesterol but are associated with myopathy. We compared the toxicity of simvastatin of C2C12 myoblasts and myotubes. Since myoblasts can proliferate and fuse to myotubes, myoblasts can be considered as satellite cells and myotubes as mature muscle fibers. Simvastatin increased plasma membrane permeability and decreased the cellular ATP content in both myoblasts and myotubes, but with a stronger effect on myoblasts. While insulin prevented cytotoxicity up to 8 h after addition of simvastatin to myotubes, prevention in myoblasts required simultaneous addition. Mevalonate and geranylgeraniol prevented simvastatin-associated cytotoxicity in both myoblasts and myotubes. Simvastatin impaired the phosphorylation of the insulin receptor (IR β), Akt ser473 and S6rp, and increased phosphorylation of AMPK thr172 in both myotubes and myoblasts, which was prevented by insulin and mevalonate. Simvastatin impaired oxygen consumption and increased superoxide production by myoblasts and myotubes and induced apoptosis via cytochrome c release. In addition, simvastatin impaired proliferation and fusion of myoblasts to myotubes by inhibiting the expression of the nuclear transcription factor MyoD and of the metalloprotease ADAM-12. Decreased expression of the proliferation factor Ki-67 and of ADAM-12 were also observed in gastrocnemius of mice treated with simvastatin. In conclusion, myoblasts were more susceptible to the toxic effects of simvastatin and simvastatin impaired myoblast proliferation and myotube formation. Impaired muscle regeneration may represent a new mechanism of statin myotoxicity.
(Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

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