Induction of BIM(EL) following growth factor withdrawal is a key event in caspase-dependent apoptosis of 661W photoreceptor cells

Eur J Neurosci. 2006 Aug;24(4):981-90. doi: 10.1111/j.1460-9568.2006.04990.x.

Abstract

Apoptosis of photoreceptor cells in the early postnatal period is a normal feature of mammalian retinal development. The role of mitochondria and caspases in the process has been well established; however, the identification of key apoptotic mediators still remains elusive. Here we report that BIM(EL), a pro-apoptotic BCL-2 family member, may be one such molecule. Following growth factor deprivation, BIM(EL) was up-regulated in mouse 661W cone photoreceptors. This event correlated with the release of mitochondrial apoptogenic factors into the cytosol, the activation of caspases and apoptosis. Moreover, a similar behaviour was observed in response to UV radiation, ionomycin or H(2)O(2) treatments. We identified the PI3K-Akt-FKHRL1 signalling cascade as the main regulatory pathway of BIM(EL) expression in these cells. Finally, using RNA interference, we were able to silence BIM(EL) expression and subsequently suppress caspase-3 activation. In conclusion, we propose BIM(EL) as a critical factor in mitochondria-dependent apoptosis of 661W photoreceptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Bcl-2-Like Protein 11
  • Caspases / metabolism*
  • Cell Line
  • Chromones / metabolism
  • Enzyme Activation
  • Enzyme Inhibitors / metabolism
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mitochondria / metabolism
  • Morpholines / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA Interference
  • Retina / cytology
  • Retina / growth & development
  • Retinal Cone Photoreceptor Cells / cytology
  • Retinal Cone Photoreceptor Cells / physiology*
  • Signal Transduction / physiology

Substances

  • Apoptosis Regulatory Proteins
  • Bcl-2-Like Protein 11
  • Bcl2l11 protein, mouse
  • Chromones
  • Enzyme Inhibitors
  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Morpholines
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Caspases