Increased Sarcolipin Expression and Decreased Sarco(endo)plasmic Reticulum Ca2+ Uptake in Skeletal Muscles of Mouse Models of Duchenne Muscular Dystrophy

Overview

Journal J Muscle Res Cell Motil

Specialties Cell Biology
Physiology

Date 2013 Jun 11

PMID 23748997

Citations 50

Authors

Joel S Schneider

Mayilvahanan Shanmugam

James Patrick Gonzalez

Henderson Lopez

Richard Gordan

Diego Fraidenraich

Gopal J Babu

Affiliations

Soon will be listed here.

Abstract

Abnormal intracellular Ca(2+) 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 Ca(2+) 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.

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