NDLI: Resveratrol induces expression of the slow, oxidative phenotype in mdx mouse muscle together with enhanced activity of the SIRT1-PGC-1 axis.

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Resveratrol induces expression of the slow, oxidative phenotype in mdx mouse muscle together with enhanced activity of the SIRT1-PGC-1 axis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Ljubicic, Vladimir Burt, Matthew Lunde, John A. Jasmin, Bernard J.
Description	Country affiliation: Canada Author Affiliation: Ljubicic V ( Department of Cellular and Molecular Medicine, Faculty of Medicine, and Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada.); Burt M ( Department of Cellular and Molecular Medicine, Faculty of Medicine, and Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada.); Lunde JA ( Department of Cellular and Molecular Medicine, Faculty of Medicine, and Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada.); Jasmin BJ ( Department of Cellular and Molecular Medicine, Faculty of Medicine, and Centre for Neuromuscular Disease, University of Ottawa, Ottawa, Ontario, Canada jasmin@uottawa.ca.)
Abstract	Slower, more oxidative muscle fibers are more resistant to the dystrophic pathology in Duchenne muscular dystrophy (DMD) patients as well as in the preclinical mdx mouse model of DMD. Therefore, one therapeutic strategy for DMD focuses on promoting expression of the slow, oxidative myogenic program. In the current study, we explored the therapeutic potential of stimulating the slow, oxidative phenotype in mdx mice by feeding 6-wk-old animals with the natural phenol resveratrol (RSV; ~100 mg·kg(-1)·day(-1)) for 6 wk. Sirtuin 1 (SIRT1) activity and protein levels increased significantly, as well as peroxisome proliferator-activated receptor-Î³ coactivator-1 (PGC-1 ) activity, in the absence of alterations in AMPK signaling. These adaptations occurred concomitant with evidence of a fast, glycolytic, to slower, more oxidative fiber type conversion, including mitochondrial biogenesis and increased expression of slower myosin heavy chain isoforms. These positive findings raised the question of whether increased exposure to RSV would result in greater therapeutic benefits. We discovered that an elevated RSV dose of ~500 mg·kg(-1)·day(-1) across a duration of 12 wk was clearly less effective at muscle remodeling in mdx mice. This treatment protocol failed to influence SIRT1 or AMPK signaling and did not result in a shift towards a slower, more oxidative phenotype. Taken together, this study demonstrates that RSV can stimulate SIRT1 and PGC-1 activation, which in turn may promote expression of the slow, oxidative myogenic program in mdx mouse muscle. The data also highlight the importance of selecting an appropriate dosage regimen of RSV to maximize its potential therapeutic effectiveness for future application in DMD patients.
File Format	HTM / HTML
ISSN	03636143
e-ISSN	15221563
DOI	10.1152/ajpcell.00357.2013
Journal	American Journal of Physiology - Cell Physiology
Issue Number	1
Volume Number	307
Language	English
Publisher	American Physiological Society
Publisher Date	2014-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Antioxidants Pharmacology Muscle Fibers, Slow-twitch Drug Effects Muscular Dystrophy, Duchenne Drug Therapy Sirtuin 1 Metabolism Stilbenes Transcription Factors Amp-activated Protein Kinases Animals Disease Models, Animal Glycolysis Mice Mice, Inbred Mdx Muscle Development Pathology Enzymology Physiopathology Oxidation-reduction Phenotype Signal Transduction Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology

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