Campus Units
Animal Science
Document Type
Article
Publication Version
Published Version
Publication Date
1-2012
Journal or Book Title
PLoS ONE
Volume
7
Issue
1
First Page
e30063
DOI
10.1371/journal.pone.0030063
Abstract
Increased utrophin expression is known to reduce pathology in dystrophin-deficient skeletal muscles. Transgenic over-expression of PGC-1α has been shown to increase levels of utrophin mRNA and improve the histology of mdx muscles. Other reports have shown that PGC-1α signaling can lead to increased oxidative capacity and a fast to slow fiber type shift. Given that it has been shown that slow fibers produce and maintain more utrophin than fast skeletal muscle fibers, we hypothesized that over-expression of PGC-1α in post-natal mdx mice would increase utrophin levels via a fiber type shift, resulting in more slow, oxidative fibers that are also more resistant to contraction-induced damage. To test this hypothesis, neonatal mdx mice were injected with recombinant adeno-associated virus (AAV) driving expression of PGC-1α. PGC-1α over-expression resulted in increased utrophin and type I myosin heavy chain expression as well as elevated mitochondrial protein expression. Muscles were shown to be more resistant to contraction-induced damage and more fatigue resistant. Sirt-1 was increased while p38 activation and NRF-1 were reduced in PGC-1α over-expressing muscle when compared to control. We also evaluated if the use a pharmacological PGC-1α pathway activator, resveratrol, could drive the same physiological changes. Resveratrol administration (100 mg/kg/day) resulted in improved fatigue resistance, but did not achieve significant increases in utrophin expression. These data suggest that the PGC-1α pathway is a potential target for therapeutic intervention in dystrophic skeletal muscle.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Copyright Owner
Selsby et al.
Copyright Date
2012
Language
en
File Format
application/pdf
Recommended Citation
Selsby, Joshua T.; Morine, Kevin J.; Pendrak, Klara; Barton, Elisabeth R.; and Sweeney, H. Lee, "Rescue of Dystrophic Skeletal Muscle by PGC-1α Involves a Fast to Slow Fiber Type Shift in the mdx Mouse" (2012). Animal Science Publications. 690.
https://lib.dr.iastate.edu/ans_pubs/690
Included in
Animal Experimentation and Research Commons, Animal Sciences Commons, Diseases Commons, Musculoskeletal, Neural, and Ocular Physiology Commons, Physiology Commons
Comments
This article is published as Selsby JT, Morine KJ, Pendrak K, Barton ER, Sweeney HL (2012) Rescue of Dystrophic Skeletal Muscle by PGC-1α Involves a Fast to Slow Fiber Type Shift in the mdx Mouse. PLoS ONE 7(1): e30063. doi: 10.1371/journal.pone.0030063.