RGD Reference Report - Alternative programs of cell death in developing retinal tissue. - Rat Genome Database

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Alternative programs of cell death in developing retinal tissue.

Authors: Guimaraes, CA  Benchimol, M  Amarante-Mendes, GP  Linden, R 
Citation: Guimaraes CA, etal., J Biol Chem. 2003 Oct 24;278(43):41938-46. Epub 2003 Aug 12.
RGD ID: 2301324
Pubmed: (View Article at PubMed) PMID:12917395
DOI: Full-text: DOI:10.1074/jbc.M306547200

We examined cell death in developing retinal tissue, following inhibition of protein synthesis, which kills undifferentiated post-mitotic cells. Ultrastructural features were found of both apoptosis and autophagy. Only approximately half of the degenerating cells were either terminal dUTP nick-end labeling (TUNEL)-positive or reacted with antibodies specific for activated caspases-3 or -9. Bongkrekic acid completely inhibited any appearance of cell death, whereas inhibitors of autophagy, caspases-9 or -3, prevented only TUNEL-positive cell death. Interestingly, inhibition of caspase-6 blocked TUNEL-negative cell death. Simultaneous inhibition of caspases-9 and -6 prevented cell death almost completely, but degeneration dependent on autophagy/caspase-9 still occurred under inhibition of both caspases-3 and -6. Thus, inhibition of protein synthesis induces in the developing retina various post-translational, mitochondria-dependent pathways of cell death. Autophagy precedes sequential activation of caspases-9 and -3, and DNA fragmentation, whereas, in parallel, caspase-6 leads to a TUNEL-negative form of cell death. Additional mechanisms of cell death may be engaged upon selective caspase inhibition.


Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Casp6  (caspase 6)

Additional Information