Bcl-2 overexpression prevents calcium overload and subsequent apoptosis in dystrophic myotubes

Biochem J. 2006 Apr 15;395(2):267-76. doi: 10.1042/BJ20051265.

Abstract

Duchenne muscular dystrophy (DMD) is a lethal disease caused by the lack of the cytoskeletal protein dystrophin. Altered calcium homoeostasis and increased calcium concentrations in dystrophic fibres may be responsible for the degeneration of muscle occurring in DMD. In the present study, we used subsarcolemmal- and mitochondrial-targeted aequorin to study the effect of the antiapoptotic Bcl-2 protein overexpression on carbachol-induced near-plasma membrane and mitochondrial calcium responses in myotubes derived from control C57 and dystrophic (mdx) mice. We show that Bcl-2 overexpression decreases subsarcolemmal and mitochondrial calcium overload that occurs during activation of nicotinic acetylcholine receptors in dystrophic myotubes. Moreover, our results suggest that overexpressed Bcl-2 protein may prevent near-plasma membrane and mitochondrial calcium overload by inhibiting IP3Rs (inositol 1,4,5-trisphosphate receptors), which we have shown previously to be involved in abnormal calcium homoeostasis in dystrophic myotubes. Most likely as a consequence, the inhibition of IP3R function by Bcl-2 also inhibits calcium-dependent apoptosis in these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Calcium / metabolism*
  • Calcium Channels
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Gene Expression
  • Inositol 1,4,5-Trisphosphate / pharmacology
  • Inositol 1,4,5-Trisphosphate Receptors
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred mdx
  • Mitochondria / metabolism
  • Muscle Fibers, Skeletal / drug effects
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle Fibers, Skeletal / pathology*
  • Muscular Dystrophy, Animal / metabolism*
  • Muscular Dystrophy, Animal / pathology*
  • Protein Transport
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Staurosporine / pharmacology

Substances

  • Calcium Channels
  • Inositol 1,4,5-Trisphosphate Receptors
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Cytoplasmic and Nuclear
  • Inositol 1,4,5-Trisphosphate
  • Staurosporine
  • Calcium