Whole body periodic acceleration is an effective therapy to ameliorate muscular dystrophy in mdx mice

Francisco Altamirano, Claudio F. Perez, Min Liu, Jeffrey Widrick, Elisabeth R. Barton, Paul D. Allen, Jose A. Adams, Jose R. Lopez

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by the absence of dystrophin in both skeletal and cardiac muscles. This leads to severe muscle degeneration, and dilated cardiomyopathy that produces patient death, which in most cases occurs before the end of the second decade. Several lines of evidence have shown that modulators of nitric oxide (NO) pathway can improve skeletal muscle and cardiac function in the mdx mouse, a mouse model for DMD. Whole body periodic acceleration (pGz) is produced by applying sinusoidal motion to supine humans and in standing conscious rodents in a headward-footward direction using a motion platform. It adds small pulses as a function of movement frequency to the circulation thereby increasing pulsatile shear stress to the vascular endothelium, which in turn increases production of NO. In this study, we examined the potential therapeutic properties of pGz for the treatment of skeletal muscle pathology observed in the mdx mouse. We found that pGz (480 cpm, 8 days, 1 hr per day) decreased intracellular Ca2+ and Na + overload, diminished serum levels of creatine kinase (CK) and reduced intracellular accumulation of Evans Blue. Furthermore, pGz increased muscle force generation and expression of both utrophin and the carboxy-terminal PDZ ligand of nNOS (CAPON). Likewise, pGz (120 cpm, 12 h) applied in vitro to skeletal muscle myotubes reduced Ca2+ and Na+ overload, diminished abnormal sarcolemmal Ca2+ entry and increased phosphorylation of endothelial NOS. Overall, this study provides new insights into the potential therapeutic efficacy of pGz as a non-invasive and non-pharmacological approach for the treatment of DMD patients through activation of the NO pathway.

Original languageEnglish (US)
Article numbere106590
JournalPLoS One
Volume9
Issue number9
DOIs
StatePublished - 2014

Fingerprint

Inbred mdx Mouse
muscular dystrophy
Muscular Dystrophies
Duchenne Muscular Dystrophy
Muscle
skeletal muscle
Skeletal Muscle
nitric oxide
therapeutics
Nitric Oxide
mice
calcium
Utrophin
animal models
dystrophin
Muscles
muscles
Evans Blue
Dystrophin
Inborn Genetic Diseases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Altamirano, F., Perez, C. F., Liu, M., Widrick, J., Barton, E. R., Allen, P. D., ... Lopez, J. R. (2014). Whole body periodic acceleration is an effective therapy to ameliorate muscular dystrophy in mdx mice. PLoS One, 9(9), [e106590]. https://doi.org/10.1371/journal.pone.0106590

Whole body periodic acceleration is an effective therapy to ameliorate muscular dystrophy in mdx mice. / Altamirano, Francisco; Perez, Claudio F.; Liu, Min; Widrick, Jeffrey; Barton, Elisabeth R.; Allen, Paul D.; Adams, Jose A.; Lopez, Jose R.

In: PLoS One, Vol. 9, No. 9, e106590, 2014.

Research output: Contribution to journalArticle

Altamirano, F, Perez, CF, Liu, M, Widrick, J, Barton, ER, Allen, PD, Adams, JA & Lopez, JR 2014, 'Whole body periodic acceleration is an effective therapy to ameliorate muscular dystrophy in mdx mice', PLoS One, vol. 9, no. 9, e106590. https://doi.org/10.1371/journal.pone.0106590
Altamirano, Francisco ; Perez, Claudio F. ; Liu, Min ; Widrick, Jeffrey ; Barton, Elisabeth R. ; Allen, Paul D. ; Adams, Jose A. ; Lopez, Jose R. / Whole body periodic acceleration is an effective therapy to ameliorate muscular dystrophy in mdx mice. In: PLoS One. 2014 ; Vol. 9, No. 9.
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