Characterization of Cell Death Pathways in Murine Retinal Neurodegeneration Implicates Cytochrome c Release, Caspase Activation, and Bid Cleavage

Characterization of Cell Death Pathways in Murine Retinal Neurodegeneration Implicates Cytochrome... Apoptosis is considered to be the final common pathway of photoreceptor cell death in different inherited retinal diseases. However, apoptosis encompasses diverse pathways of molecular interactions culminating in cellular demise. To begin dissecting these interactions, we have investigated key participants in the rd (retinal degeneration) model of retinal neurodegeneration. By Western blot analysis and immunocytochemistry, we found that cytochrome c release occurs in rd retinas concurrently with the activation of the proapoptotic protein Bid. Active forms of caspase-8 and the mitogen-activated protein kinase p38, both of which are capable of cleaving Bid, were detected in rd retinas at the peak time of photoreceptor death. In addition, the activated form of the cell death effector caspase-3 was detectable particularly at the photoreceptors in parallel with this peak degenerative phase. These data suggest that activation of both major apoptotic pathways occurs during photoreceptor degeneration in the rd mouse model of inherited blindness. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Neuroscience Elsevier

Characterization of Cell Death Pathways in Murine Retinal Neurodegeneration Implicates Cytochrome c Release, Caspase Activation, and Bid Cleavage

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Publisher
Elsevier
Copyright
Copyright © 2001 Academic Press
ISSN
1044-7431
D.O.I.
10.1006/mcne.2001.1036
Publisher site
See Article on Publisher Site

Abstract

Apoptosis is considered to be the final common pathway of photoreceptor cell death in different inherited retinal diseases. However, apoptosis encompasses diverse pathways of molecular interactions culminating in cellular demise. To begin dissecting these interactions, we have investigated key participants in the rd (retinal degeneration) model of retinal neurodegeneration. By Western blot analysis and immunocytochemistry, we found that cytochrome c release occurs in rd retinas concurrently with the activation of the proapoptotic protein Bid. Active forms of caspase-8 and the mitogen-activated protein kinase p38, both of which are capable of cleaving Bid, were detected in rd retinas at the peak time of photoreceptor death. In addition, the activated form of the cell death effector caspase-3 was detectable particularly at the photoreceptors in parallel with this peak degenerative phase. These data suggest that activation of both major apoptotic pathways occurs during photoreceptor degeneration in the rd mouse model of inherited blindness.

Journal

Molecular and Cellular NeuroscienceElsevier

Published: Oct 1, 2001

References

  • Bax, Bid and the permeabilization of the mitochondrial outer membrane in apoptosis
    Crompton, M.
  • Bid-induced conformational change of Bax is responsible for mitochondrial cytochrome c release during apoptosis
    Desagher, S.; Osen-Sand, A.; Nichols, A.; Eskes, R.; Montessuit, S.; Lauper, S.; Maundrell, K.; Antonsson, B.; Martinou, J.-C.
  • Inhibitors of p38 mitogen-activated protein kinase promote neuronal survival in vitro
    Horstmann, S.; Kahle, P.J.; Borasio, G.D.
  • SB 239063, a novel p38 inhibitor, attenuates early neuronal injury following ischemia
    Legos, J.J.; Erhardt, J.A.; White, R.F.; Lenhard, S.C.; Chandra, S.; Parsons, A.A.; Tuma, R.F.; Barone, F.C.
  • Apoptotic cell death in retinal degenerations
    Remé, C.E.; Grimm, C.; Hafezi, F.; Marti, A.; Wenzel, A.
  • Cell death: The significance of apoptosis
    Wyllie, A.H.; Kerr, J.F.; Currie, A.R.
  • Transducing signals of life and death
    Yuan, J.

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