Increased sarcolipin expression and decreased sarco(endo)plasmic reticulum Ca2+ uptake in skeletal muscles of mouse models of Duchenne muscular dystrophy

Joel S. Schneider, Mayilvahanan Shanmugam, James Patrick Gonzalez, Henderson Lopez, Richard Gordan, Diego Fraidenraich, Gopal J. Babu

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Abnormal intracellular Ca2+ handling is an important factor in the progressive functional decline of dystrophic muscle. In the present study, we investigated the function of sarco(endo)plasmic reticulum (SR) Ca 2+ ATPase (SERCA) in various dystrophic muscles of mouse models of Duchenne muscular dystrophy. Our studies show that the protein expression of sarcolipin, a key regulator of the SERCA pump is abnormally high and correlates with decreased maximum velocity of SR Ca2+ uptake in the soleus, diaphragm and quadriceps of mild (mdx) and severe (mdx:utr-/-) dystrophic mice. These changes are more pronounced in the muscles of mdx:utr-/- mice. We also found increased expression of SERCA2a and calsequestrin specifically in the dystrophic quadriceps. Immunostaining analysis further showed that SERCA2a expression is associated both with fibers expressing slow-type myosin and regenerating fibers expressing embryonic myosin. Together, our data suggest that sarcolipin upregulation is a common secondary alteration in all dystrophic muscles and contributes to the abnormal elevation of intracellular Ca 2+ concentration via SERCA inhibition.

Original languageEnglish (US)
Pages (from-to)349-356
Number of pages8
JournalJournal of Muscle Research and Cell Motility
Volume34
Issue number5-6
DOIs
StatePublished - Dec 1 2013

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology
  • Cell Biology

Keywords

  • Ca uptake
  • Duchenne muscular dystrophy
  • Fiber-type
  • SERCA
  • Sarcolipin
  • Skeletal muscle

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