Document Detail


Coenzyme Q10 reverses mitochondrial dysfunction in atorvastatin-treated mice and increases exercise endurance.
MedLine Citation:
PMID:  22653988     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Statins are cholesterol-lowering drugs widely used in the prevention of cardiovascular diseases; however, they are associated with various types of myopathies. Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase and thus decrease biosynthesis of low-density lipoprotein cholesterol and may also reduce ubiquinones, essential coenzymes of a mitochondrial electron transport chain, which contain isoprenoid residues, synthesized through an HMG-CoA reductase-dependent pathway. Therefore, we hypothesized that statin treatment might influence physical performance through muscular mitochondrial dysfunction due to ubiquinone deficiency. The effect of two statins, atorvastatin and pravastatin, on ubiquinone content, mitochondrial function, and physical performance was examined by using statin-treated mice. Changes in energy metabolism in association with statin treatment were studied by using cultured myocytes. We found that atorvastatin-treated mice developed muscular mitochondrial dysfunction due to ubiquinone deficiency and a decrease in exercise endurance without affecting muscle mass and strength. Meanwhile, pravastatin at ten times higher dose of atorvastatin had no such effects. In cultured myocytes, atorvastatin-related decrease in mitochondrial activity led to a decrease in oxygen utilization and an increase in lactate production. Conversely, coenzyme Q(10) treatment in atorvastatin-treated mice reversed atorvastatin-related mitochondrial dysfunction and a decrease in oxygen utilization, and thus improved exercise endurance. Atorvastatin decreased exercise endurance in mice through mitochondrial dysfunction due to ubiquinone deficiency. Ubiquinone supplementation with coenzyme Q(10) could reverse atorvastatin-related mitochondrial dysfunction and decrease in exercise tolerance.
Authors:
Ayako Muraki; Kazutoshi Miyashita; Masanori Mitsuishi; Masanori Tamaki; Kumiko Tanaka; Hiroshi Itoh
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-31
Journal Detail:
Title:  Journal of applied physiology (Bethesda, Md. : 1985)     Volume:  113     ISSN:  1522-1601     ISO Abbreviation:  J. Appl. Physiol.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-08-02     Completed Date:  2013-01-08     Revised Date:  2013-09-26    
Medline Journal Info:
Nlm Unique ID:  8502536     Medline TA:  J Appl Physiol (1985)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  479-86     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
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MeSH Terms
Descriptor/Qualifier:
Animals
Heptanoic Acids / antagonists & inhibitors,  pharmacology*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Lactic Acid / biosynthesis
Male
Mice
Mice, Inbred C57BL
Mitochondria, Muscle / drug effects*
Muscle Cells / drug effects
Muscle Strength / drug effects
Muscle, Skeletal / anatomy & histology,  drug effects
Organ Size / drug effects
Oxygen Consumption / drug effects
Physical Conditioning, Animal / physiology*
Physical Endurance / drug effects*
Pravastatin / pharmacology
Pyrroles / antagonists & inhibitors,  pharmacology*
Ubiquinone / analogs & derivatives*,  analysis,  pharmacology
Chemical
Reg. No./Substance:
0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Pyrroles; 1339-63-5/Ubiquinone; 303-98-0/coenzyme Q10; 50-21-5/Lactic Acid; 81093-37-0/Pravastatin; A0JWA85V8F/atorvastatin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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