You are not logged in.
Openly accessible

Statin-induced increases in atrophy gene expression occur independently of changes in PGC1α protein and mitochondrial content

Goodman, Craig A., Pol, Derk, Zacharewicz, Evelyn, Lee-Young, Robert S., Snow, Rod J., Russell, Aaron P. and McConell, Glenn K. 2015, Statin-induced increases in atrophy gene expression occur independently of changes in PGC1α protein and mitochondrial content, PLoS one, vol. 10, no. 5, pp. 1-18, doi: 10.1371/journal.pone.0128398.

Attached Files
Name Description MIMEType Size Downloads
zacharewicz-statininduced-2015.pdf Published version application/pdf 687.87KB 7

Title Statin-induced increases in atrophy gene expression occur independently of changes in PGC1α protein and mitochondrial content
Author(s) Goodman, Craig A.
Pol, Derk
Zacharewicz, Evelyn
Lee-Young, Robert S.
Snow, Rod J.ORCID iD for Snow, Rod J. orcid.org/0000-0002-4796-6916
Russell, Aaron P.ORCID iD for Russell, Aaron P. orcid.org/0000-0002-7323-9501
McConell, Glenn K.
Journal name PLoS one
Volume number 10
Issue number 5
Start page 1
End page 18
Total pages 18
Publisher Public Library of Science (PLoS)
Place of publication San Francisco, Calif.
Publication date 2015
ISSN 1932-6203
Keyword(s) Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
NITRIC-OXIDE SYNTHASE
COA REDUCTASE INHIBITORS
AMYOTROPHIC-LATERAL-SCLEROSIS
FOXO TRANSCRIPTION FACTORS
SKELETAL-MUSCLE ATROPHY
INDUCED MYOPATHY
UP-REGULATION
IN-VIVO
LIPOPROTEIN-LIPASE
UBIQUITIN LIGASES
Summary One serious side effect of statin drugs is skeletal muscle myopathy. Although the mechanism(s) responsible for statin myopathy remains to be fully determined, an increase in muscle atrophy gene expression and changes in mitochondrial content and/or function have been proposed to play a role. In this study, we examined the relationship between statin-induced expression of muscle atrophy genes, regulators of mitochondrial biogenesis, and markers of mitochondrial content in slow- (ST) and fast-twitch (FT) rat skeletal muscles. Male Sprague Dawley rats were treated with simvastatin (60 or 80 mg·kg(-1)·day(-1)) or vehicle control via oral gavage for 14 days. In the absence of overt muscle damage, simvastatin treatment induced an increase in atrogin-1, MuRF1 and myostatin mRNA expression; however, these were not associated with changes in peroxisome proliferator gamma co-activator 1 alpha (PGC-1α) protein or markers of mitochondrial content. Simvastatin did, however, increase neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and AMPK α-subunit protein expression, and tended to increase total NOS activity, in FT but not ST muscles. Furthermore, simvastatin induced a decrease in β-hydroxyacyl CoA dehydrogenase (β-HAD) activity only in FT muscles. These findings suggest that the statin-induced activation of muscle atrophy genes occurs independent of changes in PGC-1α protein and mitochondrial content. Moreover, muscle-specific increases in NOS expression and possibly NO production, and decreases in fatty acid oxidation, could contribute to the previously reported development of overt statin-induced muscle damage in FT muscles.
Language eng
DOI 10.1371/journal.pone.0128398
Field of Research 111199 Nutrition and Dietetics not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Public Library of Science (PLoS)
Free to Read? Yes
Use Rights Creative Commons Attribution licence
Persistent URL http://hdl.handle.net/10536/DRO/DU:30078400

Document type: Journal Article
Collections: School of Exercise and Nutrition Sciences
Open Access Collection
Connect to link resolver
 
Unless expressly stated otherwise, the copyright for items in DRO is owned by the author, with all rights reserved.

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.

Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 7 times in TR Web of Science
Scopus Citation Count Cited 6 times in Scopus
Google Scholar Search Google Scholar
Access Statistics: 107 Abstract Views, 8 File Downloads  -  Detailed Statistics
Created: Tue, 06 Oct 2015, 07:54:14 EST

Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.