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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Combined Effect of AMPK/PPAR Agonists and Exercise Training in mdx Mice Functional Performance

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Author(s):
Bueno Junior, Carlos R. [1] ; Pantaleao, Lucas C. [2] ; Voltarelli, Vanessa A. [3] ; Bozi, Luiz Henrique M. [3] ; Brum, Patricia Chakur [3] ; Zatz, Mayana [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Inst Biosci, Human Genome Res Ctr, Sao Paulo - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, Sao Paulo - Brazil
[3] Univ Sao Paulo, Sch Phys Educ & Sport, Sao Paulo - Brazil
Total Affiliations: 3
Document type: Journal article
Source: PLoS One; v. 7, n. 9 SEP 21 2012.
Web of Science Citations: 28
Abstract

The present investigation was undertaken to test whether exercise training (ET) associated with AMPK/PPAR agonists (EM) would improve skeletal muscle function in mdx mice. These drugs have the potential to improve oxidative metabolism. This is of particular interest because oxidative muscle fibers are less affected in the course of the disease than glycolitic counterparts. Therefore, a cohort of 34 male congenic C57Bl/10J mdx mice included in this study was randomly assigned into four groups: vehicle solution (V), EM {[}AICAR (AMPK agonist, 50 mg/Kg-1.day-1, ip) and GW 1516 (PPAR delta agonist, 2.5 mg/Kg-1.day-1, gavage)], ET (voluntary running on activity wheel) and EM+ET. Functional performance (grip meter and rotarod), aerobic capacity (running test), muscle histopathology, serum creatine kinase (CK), levels of ubiquitined proteins, oxidative metabolism protein expression (AMPK, PPAR, myoglobin and SCD) and intracellular calcium handling (DHPR, SERCA and NCX) protein expression were analyzed. Treatments started when the animals were two months old and were maintained for one month. A significant functional improvement (p<0.05) was observed in animals submitted to the combination of ET and EM. CK levels were decreased and the expression of proteins related to oxidative metabolism was increased in this group. There were no differences among the groups in the intracellular calcium handling protein expression. To our knowledge, this is the first study that tested the association of ET with EM in an experimental model of muscular dystrophy. Our results suggest that the association of ET and EM should be further tested as a potential therapeutic approach in muscular dystrophies. (AU)

FAPESP's process: 98/14254-2 - The Human Genome Research Center
Grantee:Mayana Zatz
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC