PUBLICATION
Coenzyme Q10 protects against statin-induced myotoxicity in zebrafish larvae (Danio rerio)
- Authors
- Pasha, R., Moon, T.W.
- ID
- ZDB-PUB-170418-2
- Date
- 2017
- Source
- Environmental Toxicology and Pharmacology 52: 150-160 (Journal)
- Registered Authors
- Keywords
- CoQ10, Larvae, Mitochondria, Muscle atrophy, Myotoxicity, Zebrafish
- MeSH Terms
-
- Atorvastatin/toxicity*
- Muscle Proteins/genetics
- Hydroxymethylglutaryl-CoA Reductase Inhibitors/toxicity*
- Animals
- Locomotion/drug effects
- Zebrafish Proteins/genetics
- RNA, Messenger/metabolism
- Muscular Diseases/chemically induced*
- Muscular Diseases/genetics
- Larva
- Protective Agents/pharmacology*
- F-Box Proteins/genetics
- Ubiquinone/analogs & derivatives*
- Ubiquinone/pharmacology
- Zebrafish
- Transcription Factors/genetics
- PubMed
- 28414942 Full text @ Environ. Toxicol. Pharmacol.
Citation
Pasha, R., Moon, T.W. (2017) Coenzyme Q10 protects against statin-induced myotoxicity in zebrafish larvae (Danio rerio). Environmental Toxicology and Pharmacology. 52:150-160.
Abstract
3-Hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme of the mevalonic acid pathway and is required for cholesterol biosynthesis and the synthesis of Coenzyme Q10 (CoQ10). Statins inhibit HMGCR, thus inhibiting the downstream products of this pathway including the biosynthesis of decaprenyl-pyrophosphate that is critical for the synthesis of Coenzyme Q10 (CoQ10). We show that zebrafish (Danio rerio) larvae treated in tank water with Atorvastatin (ATV; Lipitor) exhibited movement alterations and reduced whole body tissue metabolism. The ATV-inhibition of HMGCR function altered transcript abundance of muscle atrophy markers (atrogen-1, murf) and the mitochondrial biogenesis marker (pgc-1?). Furthermore, ATV-induced reduction in larval response to tactile stimuli was reversed with treatment of CoQ10. Together, the implication of our results contributes to the understanding of the mechanisms of action of the statin-induced damage in this model fish species.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping