Caspase-independent photoreceptor apoptosis in vivo and differential expression of apoptotic protease activating factor-1 and caspase-3 during retinal development
| Autor: | Maryanne Donovan, Thomas G. Cotter |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Retinal degeneration
Light Apoptosis Cytochrome c Group Caspase 3 Cysteine Proteinase Inhibitors Retina Photoreceptor cell Amino Acid Chloromethyl Ketones Diltiazem Mice chemistry.chemical_compound medicine Animals Photoreceptor Cells Molecular Biology Caspase biology Calpain Cytochrome c Intrinsic apoptosis Proteins Retinal Cell Biology Calcium Channel Blockers medicine.disease Caspase Inhibitors Cell biology Apoptotic Protease-Activating Factor 1 medicine.anatomical_structure chemistry Caspases Protein Biosynthesis biology.protein Calcium |
| Zdroj: | Cell Death & Differentiation. 9:1220-1231 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/sj.cdd.4401105 |
| Popis: | Apoptosis is the mode of photoreceptor cell death in many retinal dystrophies. Exposure of Balb/c mice to excessive levels of light induces photoreceptor apoptosis and represents an animal model for the study of retinal degenerations. Caspases have emerged as central regulators of apoptosis, executing this tightly controlled death pathway in many cells. Previously we have reported that light-induced photoreceptor apoptosis occurs independently of one the key executioners of apoptosis, caspase-3. This present study extends these results reporting on the lack of activation of other caspases in this model including caspases-8, -9, -7, and -1. Furthermore, photoreceptor apoptosis cannot be inhibited with the broad range caspase inhibitor zVAD-fmk indicating that light-induced retinal degeneration is caspase-independent. We demonstrate that cytochrome c does not translocate from mitochondria to the cytosol during photoreceptor apoptosis. We also show that during retinal development apoptotic protease activating factor (Apaf-1) protein levels are markedly decreased and this is associated with the inability to activate the mitochondrial caspase cascade in the mature retina. In addition, there is also a significant reduction in expression of caspases-3 and -9 during retinal maturation and these levels do not increase following light exposure. Finally, we show that the calcium-dependent proteases calpains are active during light-induced retinal degeneration and establish that the calcium channel blocker D-cis-diltiazem completely inhibits photoreceptor apoptosis. |
| Databáze: | OpenAIRE |
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