Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
References
Ahn SG, Thiele DJ (2003) Redox regulation of mammalian heat shock factor 1 is essential for Hsp gene activation and protection from stress. Genes Dev 17:516–528. https://doi.org/10.1101/gad.1044503
Almada AE, Wagers AJ (2016) Molecular circuitry of stem cell fate in skeletal muscle regeneration, ageing and disease. Nat Rev Mol Cell Biol 17:267–279. https://doi.org/10.1038/nrm.2016.7
Baumann CW, Otis JS (2015) 17-(allylamino)-17-demethoxygeldanamycin drives Hsp70 expression but fails to improve morphological or functional recovery in injured skeletal muscle. Clin Exp Pharmacol Physiol 42:1308–1316. https://doi.org/10.1111/1440-1681.12477
Baumann CW, Rogers RG, Otis JS (2016) Utility of 17-(allylamino)-17-demethoxygeldanamycin treatment for skeletal muscle injury. Cell Stress Chaperones 21:1111–1117. https://doi.org/10.1007/s12192-016-0717-1
Chung J et al (2008) HSP72 protects against obesity-induced insulin resistance. Proc Natl Acad Sci USA 105:1739–1744. https://doi.org/10.1073/pnas.0705799105
Conde AG, Lau SS, Dillmann WH, Mestril R (1997) Induction of heat shock proteins by tyrosine kinase inhibitors in rat cardiomyocytes and myogenic cells confers protection against simulated ischemia. J Mol Cell Cardiol 29:1927–1938
Conte TC et al (2008) Radicicol improves regeneration of skeletal muscle previously damaged by crotoxin in mice. Toxicon 52:146–155. https://doi.org/10.1016/j.toxicon.2008.04.177
Conte TC et al (2012) The beta2-adrenoceptor agonist formoterol improves structural and functional regenerative capacity of skeletal muscles from aged rat at the early stages of postinjury. J Gerontol A Biol Sci Med Sci 67:443–455. https://doi.org/10.1093/gerona/glr195
Frydman J (2001) Folding of newly translated proteins in vivo: the role of molecular chaperones. Annu Rev Biochem 70:603–647
Gehrig SM et al (2012) Hsp72 preserves muscle function and slows progression of severe muscular dystrophy. Nature 484:394–398. https://doi.org/10.1038/nature10980
Gombos I et al (2011) Membrane-lipid therapy in operation: the HSP co-inducer BGP-15 activates stress signal transduction pathways by remodeling plasma membrane rafts. PLoS One 6:e28818. https://doi.org/10.1371/journal.pone.0028818
Gomez-Cabrera MC, Close GL, Kayani A, McArdle A, Vina J, Jackson MJ (2010) Effect of xanthine oxidase-generated extracellular superoxide on skeletal muscle force generation. Am J Physiol Regul Integr Comp Physiol 298:R2-8. https://doi.org/10.1152/ajpregu.00142.2009
Griffin TM, Valdez TV, Mestril R (2004) Radicicol activates heat shock protein expression and cardioprotection in neonatal rat cardiomyocytes. Am J Physiol Heart Circ Physiol 287:H1081-1088. https://doi.org/10.1152/ajpheart.00921.2003
Gungor B et al (2014) Rac1 participates in thermally induced alterations of the cytoskeleton, cell morphology and lipid rafts, and regulates the expression of heat shock proteins in B16F10 melanoma cells. PLoS One 9:e89136. https://doi.org/10.1371/journal.pone.0089136
Hawke TJ, Garry DJ (2001) Myogenic satellite cells: physiology to molecular biology. J Appl Physiol (1985) 91:534–551
Henstridge DC et al (2014) Activating HSP72 in rodent skeletal muscle increases mitochondrial number and oxidative capacity and decreases insulin resistance. Diabetes 63:1881–1894. https://doi.org/10.2337/db13-0967
Jerkovic R, Argentini C, Serrano-Sanchez A, Cordonnier C, Schiaffino S (1997) Early myosin switching induced by nerve activity in regenerating slow skeletal muscle. Cell Struct Funct 22:147–153
Kayani AC, Close GL, Broome CS, Jackson MJ, McArdle A (2008) Enhanced recovery from contraction-induced damage in skeletal muscles of old mice following treatment with the heat shock protein inducer 17-(allylamino)-17-demethoxygeldanamycin. Rejuvenation Res 11:1021–1030. https://doi.org/10.1089/rej.2008.0795
Kennedy TL et al (2016) BGP-15 improves aspects of the dystrophic pathology in mdx and dko mice with differing efficacies in heart and skeletal muscle. Am J Pathol 186:3246–3260
Kultz D (2005) Molecular and evolutionary basis of the cellular stress response. Annu Rev Physiol 67:225–257. https://doi.org/10.1146/annurev.physiol.67.040403.103635
Macario AJ, Conway de Macario E (2007) Molecular chaperones: multiple functions, pathologies, and potential applications. Front Biosci 12:2588–2600
Miyabara EH, Martin JL, Griffin TM, Moriscot AS, Mestril R (2006) Overexpression of inducible 70-kDa heat shock protein in mouse attenuates skeletal muscle damage induced by cryolesioning. Am J Physiol Cell Physiol 290:C1128-1138
Miyabara EH et al (2010) Mammalian target of rapamycin complex 1 is involved in differentiation of regenerating myofibers in vivo. Muscle Nerve 42:778–787. https://doi.org/10.1002/mus.21754
Miyabara EH et al (2012) Overexpression of inducible 70-kDa heat shock protein in mouse improves structural and functional recovery of skeletal muscles from atrophy. Pflugers Arch 463:733–741. https://doi.org/10.1007/s00424-012-1087-x
Morimoto RI (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12:3788–3796
Naghdi S, Hajnoczky G (2016) VDAC2-specific cellular functions and the underlying structure. Biochim Biophys Acta 1863:2503–2514. https://doi.org/10.1016/j.bbamcr.2016.04.020
Neckers L (2002) Hsp90 inhibitors as novel cancer chemotherapeutic agents. Trends Mol Med 8:S55-61
Neckers L, Workman P (2012) Hsp90 molecular chaperone inhibitors: are we there yet? Clin Cancer Res 18:64–76. https://doi.org/10.1158/1078-0432.CCR-11-1000
Ogata T, Oishi Y, Roy RR, Ohmori H (2003) Endogenous expression and developmental changes of HSP72 in rat skeletal muscles. J Appl Physiol (1985) 95:1279–1286. https://doi.org/10.1152/japplphysiol.00353.2003
Oki K, Wiseman RW, Breedlove SM, Jordan CL (2013) Androgen receptors in muscle fibers induce rapid loss of force but not mass: implications for spinal bulbar muscular atrophy. Muscle Nerve 47:823–834. https://doi.org/10.1002/mus.23813
Pereira MG, Baptista IL, Carlassara EO, Moriscot AS, Aoki MS, Miyabara EH (2014a) Leucine supplementation improves skeletal muscle regeneration after cryolesion in rats. PLoS One 9:e85283. https://doi.org/10.1371/journal.pone.0085283
Pereira MG et al (2014b) Leucine supplementation accelerates connective tissue repair of injured tibialis anterior muscle. Nutrients 6:3981–4001. https://doi.org/10.3390/nu6103981
Pereira MG, Silva MT, da Cunha FM, Moriscot AS, Aoki MS, Miyabara EH (2015) Leucine supplementation improves regeneration of skeletal muscles from old rats. Exp Gerontol 72:269–277. https://doi.org/10.1016/j.exger.2015.10.006
Ramamurthy B, Hook P, Jones AD, Larsson L (2001) Changes in myosin structure and function in response to glycation. FASEB J 15:2415–2422. https://doi.org/10.1096/fj.01-0183com
Roe SM, Prodromou C, O’Brien R, Ladbury JE, Piper PW, Pearl LH (1999) Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. J Med Chem 42:260–266. https://doi.org/10.1021/jm980403y
Salah H et al (2016) The chaperone co-inducer BGP-15 alleviates ventilation-induced diaphragm dysfunction. Sci Transl Med 8:350ra103. https://doi.org/10.1126/scitranslmed.aaf7099
Senf SM (2013) Skeletal muscle heat shock protein 70: diverse functions and therapeutic potential for wasting disorders. Front Physiol 4:330. https://doi.org/10.3389/fphys.2013.00330
Silva MT, Wensing LA, Brum PC, Camara NO, Miyabara EH (2014) Impaired structural and functional regeneration of skeletal muscles from beta2-adrenoceptor knockout mice. Acta Physiol (Oxf) 211:617–633. https://doi.org/10.1111/apha.12329
Soti C, Nagy E, Giricz Z, Vigh L, Csermely P, Ferdinandy P (2005) Heat shock proteins as emerging therapeutic targets. Br J Pharmacol 146:769–780
Sottile ML, Nadin SB (2017) Heat shock proteins and DNA repair mechanisms: an updated overview. Cell Stress Chaperones. https://doi.org/10.1007/s12192-017-0843-4
Vigh L, Horvath I, Maresca B, Harwood JL (2007) Can the stress protein response be controlled by ‘membrane-lipid therapy’? Trends Biochem Sci 32:357–363
Wagatsuma A et al (2011) Pharmacological inhibition of HSP90 activity negatively modulates myogenic differentiation and cell survival in C2C12 cells. Mol Cell Biochem 358:265–280. https://doi.org/10.1007/s11010-011-0977-0
Westerheide SD, Anckar J, Stevens SM Jr, Sistonen L, Morimoto RI (2009) Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science 323:1063–1066. https://doi.org/10.1126/science.1165946
Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM (1994) Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc Natl Acad Sci USA 91:8324–8328
Yin H, Price F, Rudnicki MA (2013) Satellite cells and the muscle stem cell niche. Physiol Rev 93:23–67. https://doi.org/10.1152/physrev.00043.2011
Zou J, Guo Y, Guettouche T, Smith DF, Voellmy R (1998) Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 94:471–480
Acknowledgements
The authors thank Dr. Anselmo S. Moriscot for allowing the use of the cryostat from his laboratory.
Funding
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).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that there are no conflicts of interest associated with this study.
Rights and permissions
About this article
Cite this article
Nascimento, T.L., Silva, M.T. & Miyabara, E.H. BGP-15 improves contractile function of regenerating soleus muscle. J Muscle Res Cell Motil 39, 25–34 (2018). https://doi.org/10.1007/s10974-018-9495-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10974-018-9495-y