Alternative programs of cell death in developing retinal tissue.
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.
Guimarães
Cinthya A
CA
Instituto de Biofísica, Universidade Federal do Rio de Janeiro, CCS bloco G, Cidade Universitária, 21949-900 Rio de Janeiro, Brazil.
Benchimol
Marlene
M
Amarante-Mendes
Gustavo P
GP
Linden
Rafael
R
D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D017209:Apoptosis; D001343:Autophagy; D053148:Caspase 3; D053178:Caspase 6; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D016923:Cell Death; D053938:DNA Fragmentation; D020287:In Situ Nick-End Labeling; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012160:Retina / Q000166:cytology* / Q000254:growth & development; D015398:Signal Transduction
D011500:Protein Synthesis Inhibitors; D000841:Anisomycin; C505410:Casp3 protein, rat; C505518:Casp6 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053178:Caspase 6; D053453:Caspase 9; D020169:Caspases