Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.1.3 (
ATPase
)
65,361
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Reduction in the expression of sarcolipin (SLN), an inhibitor of sarco(endo)plasmic reticulum (SR) Ca
2+
-
ATPase
(SERCA), ameliorates severe muscular dystrophy in mice. However, the mechanism by which SLN inhibition improves muscle structure remains unclear. Here, we describe the previously unknown function of SLN in muscle differentiation in Duchenne muscular dystrophy (DMD). Overexpression of SLN in C
2
C
12
resulted in decreased SERCA pump activity, reduced SR Ca
2+
load, and increased intracellular Ca
2+
(
Ca
i
2+
) concentration. In addition, SLN overexpression resulted in altered expression of myogenic markers and poor myogenic differentiation. In
dystrophin
-deficient dog myoblasts and myotubes, SLN expression was significantly high and associated with defective
Ca
i
2+
cycling. The dystrophic dog myotubes were less branched and associated with decreased autophagy and increased expression of mitochondrial fusion and fission proteins. Reduction in SLN expression restored these changes and enhanced dystrophic dog myoblast fusion during differentiation. In summary, our data suggest that SLN upregulation is an intrinsic secondary change in
dystrophin
-deficient myoblasts and could account for the
Ca
i
2+
mishandling, which subsequently contributes to poor myogenic differentiation. Accordingly, reducing SLN expression can improve the
Ca
i
2+
cycling and differentiation of dystrophic myoblasts. These findings provide cellular-level supports for targeting SLN expression as a therapeutic strategy for DMD.
...
PMID:Sarcolipin overexpression impairs myogenic differentiation in Duchenne muscular dystrophy. 3136 91
<< Previous
1
2
3
4
5
