PMID- 12917395
OWN - NLM
STAT- MEDLINE
DCOM- 20040105
LR  - 20230815
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 278
IP  - 43
DP  - 2003 Oct 24
TI  - Alternative programs of cell death in developing retinal tissue.
PG  - 41938-46
AB  - 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.
FAU - Guimaraes, Cinthya A
AU  - Guimaraes CA
AD  - Instituto de Biofisica, Universidade Federal do Rio de Janeiro, CCS bloco G, 
      Cidade Universitaria, 21949-900 Rio de Janeiro, Brazil.
FAU - Benchimol, Marlene
AU  - Benchimol M
FAU - Amarante-Mendes, Gustavo P
AU  - Amarante-Mendes GP
FAU - Linden, Rafael
AU  - Linden R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030812
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 6C74YM2NGI (Anisomycin)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Casp6 protein, rat)
RN  - EC 3.4.22.- (Casp9 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 6)
RN  - EC 3.4.22.- (Caspase 9)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Animals
MH  - Anisomycin/pharmacology
MH  - *Apoptosis
MH  - *Autophagy
MH  - Caspase 3
MH  - Caspase 6
MH  - Caspase 9
MH  - Caspases/metabolism
MH  - Cell Death
MH  - DNA Fragmentation
MH  - In Situ Nick-End Labeling
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - Rats
MH  - Rats, Inbred Strains
MH  - Retina/*cytology/growth & development
MH  - Signal Transduction
EDAT- 2003/08/15 05:00
MHDA- 2004/01/06 05:00
CRDT- 2003/08/15 05:00
PHST- 2003/08/15 05:00 [pubmed]
PHST- 2004/01/06 05:00 [medline]
PHST- 2003/08/15 05:00 [entrez]
AID - S0021-9258(20)82726-4 [pii]
AID - 10.1074/jbc.M306547200 [doi]
PST - ppublish
SO  - J Biol Chem. 2003 Oct 24;278(43):41938-46. doi: 10.1074/jbc.M306547200. Epub 2003 
      Aug 12.