BGP-15 improves contractile function of regenerating soleus muscle
This study investigated the effect of the heat shock protein inducer O-[3-piperidino-2-hydroxy-1-propyl]-nicotinic amidoxime (BGP-15) on the morphology and contractile function of regenerating soleus muscles from mice. Cryolesioned soleus muscles from young mice treated daily with BGP-15 (15 mg/Kg) were evaluated on post-cryolesion day 10. At this time point, there was a significant decrease in the cross-sectional area of regenerating myofibers, maximal force, specific tetanic force, and fatigue resistance of regenerating soleus muscles. BGP-15 did not reverse the decrease in myofiber cross-sectional area but effectively prevented the reduction in tetanic force and fatigue resistance of regenerating muscles. In addition, BGP-15 treatment increased the expression of embryonic myosin heavy chain (e-MyHC), MyHC-II and MyHC-I in regenerating muscles. Although BGP-15 did not alter voltage dependent anion-selective channel 2 (VDAC2) expression in cryolesioned muscles, it was able to increase inducible 70-kDa heat shock protein (HSP70) expression. Our results suggest that BGP-15 improves strength recovery in regenerating soleus muscles by accelerating the re-expression of adult MyHC-II and MyHC-I isoforms and HSP70 induction. The beneficial effects of BGP-15 on the contractile function of regenerating muscles reinforce the potential of this molecule to be used as a therapeutic agent.
KeywordsBGP-15 Heat shock proteins Skeletal muscle regeneration Muscle contraction
The authors thank Dr. Anselmo S. Moriscot for allowing the use of the cryostat from his laboratory.
This study was funded by São Paulo Research Foundation (FAPESP) (Grant No. 14/23391-8) and National Council for Scientific and Technological Development (CNPq) (Fellowship/Grant No. 305869/2015-9). Tábata L. Nascimento received a Ph.D. fellowship from FAPESP (Grant No. 13/04783-0). Meiricris T. Silva received a post-doctoral fellowship from FAPESP/CAPES (Grant No. 14/13874-1).
Compliance with ethical standards
Conflict of interest
The authors declare that there are no conflicts of interest associated with this study.
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