Bim Expression Indicates the Pathway to Retinal Cell Death in Development and Degeneration
| Autor: | Philippe Bouillet, Francesca Doonan, Violeta Gómez-Vicente, Thomas G. Cotter, Maryanne Donovan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Gene isoform
Retinal degeneration Programmed cell death Retina chemistry.chemical_compound Mice Downregulation and upregulation Proto-Oncogene Proteins medicine In Situ Nick-End Labeling Animals Enzyme Inhibitors Caspase Calcimycin Mice Knockout biology Bcl-2-Like Protein 11 Cell Death Ionophores General Neuroscience Retinal Degeneration Gene Expression Regulation Developmental Membrane Proteins Retinal Articles Hydrogen Peroxide medicine.disease Staurosporine Caspase 9 Mice Mutant Strains Cell biology Mice Inbred C57BL medicine.anatomical_structure chemistry Apoptosis biology.protein biological phenomena cell phenomena and immunity Apoptosis Regulatory Proteins |
| Popis: | Programmed cell death (PCD) during development of the mouse retina involves activation of the mitochondrial pathway. Previous work has shown that the multidomain Bcl-2 family proteins Bax and Bak are fundamentally involved in this process. To induce mitochondrial membrane permeabilization, Bax and Bak require that prosurvival members of the family be inactivated by binding of “BH3-only” members. We showed previously that the BH3-only protein BimEL is highly expressed during postnatal retinal development but decreases dramatically thereafter. The purpose of this study was to investigate a possible role for Bim, in retinal development and degeneration, upstream of Bax and Bak.Bim−/−mice analyzed for defective retinal development exhibit an increase in retinal thickness and a delay in PCD, thereby confirming a role for Bim. We also demonstrate that in response to certain death stimuli,bim+/+retinal explants upregulate BimEL leading to caspase activation and cell death, whereasbim−/−explants are resistant to apoptosis. Finally, we analyzed Bim expression in the retinal degeneration (rd) mouse, anin vivomodel of retinal degeneration. Bim isoforms, which decrease during development, are not reexpressed during retinal degeneration and ultimately photoreceptor cells die by a caspase-independent mechanism. Thus, we conclude that in cases in which BimEL is reexpressed during pathological cell death, developmental cell death pathways are reactivated. However, the absence of BimEL expression correlates with caspase-independent death in the rd model. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|