PMID- 8603926
OWN - NLM
STAT- MEDLINE
DCOM- 19960516
LR  - 20190508
IS  - 0021-9525 (Print)
IS  - 1540-8140 (Electronic)
IS  - 0021-9525 (Linking)
VI  - 132
IP  - 5
DP  - 1996 Mar
TI  - Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation 
      of embryonal stem cells.
PG  - 955-68
AB  - We report here that all trans-retinoic acid (RA), a classical morphogen, induces 
      apoptosis during the neural differentiation of the embryonic stem cell line P19. 
      The apoptotic cells showed, in addition to DNA cleavage, typical morphological 
      changes including chromatin condensation, nuclear fragmentation, and cytoplasmic 
      vacuolation. These apoptotic changes became obvious by 12 h after the addition of 
      RA. The endogenous expression of bcl-2 in surviving cells was down-regulated 
      during this process, and the compelled expression of bcl-2 by retroviral vectors 
      reduced the number of apoptotic cells. Apoptosis was partially inhibited by 
      adding antisense oligonucleotides against RA receptors (RARs) simultaneously or 
      by transfecting a plasmid vector flanked with a RA-responsive element. Antisense 
      oligonucleotides against retinoid X receptors (RXRs), the receptors for 9 cis-RA, 
      did not inhibit apoptosis induced by all trans-RA. Cycloheximide and actinomycin 
      D, inhibitors of protein and RNA syntheses, respectively, suppressed apoptosis. 
      No changes were seen in the expression of tumor necrosis factors, their 
      receptors, Fas, FasL, p53, or c-myc, molecules which have been suggested to 
      participate in the apoptotic process. Addition of neurotrophins to the culture 
      medium did not affect apoptosis. These findings suggest that the signals 
      themselves, promote expression of molecules essential for apoptosis. Furthermore, 
      we observed that RA induced apoptosis of cerebral neurons from murine embryos in 
      primary culture, which suggests that RA might participate in cell death which 
      occurs during neural development.
FAU - Okazawa, H
AU  - Okazawa H
AD  - Department of Neurology, Faculty of Medicine, University of Tokyo, Japan.
FAU - Shimizu, J
AU  - Shimizu J
FAU - Kamei, M
AU  - Kamei M
FAU - Imafuku, I
AU  - Imafuku I
FAU - Hamada, H
AU  - Hamada H
FAU - Kanazawa, I
AU  - Kanazawa I
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Cell Biol
JT  - The Journal of cell biology
JID - 0375356
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Base Sequence
MH  - Blotting, Northern
MH  - Brain/cytology
MH  - Cell Differentiation
MH  - Cell Line
MH  - Gene Expression Regulation, Developmental
MH  - Genetic Vectors
MH  - Mice
MH  - Molecular Sequence Data
MH  - Nervous System/cytology/drug effects
MH  - *Nervous System Physiological Phenomena
MH  - Neurons/drug effects/pathology
MH  - Oligonucleotides, Antisense
MH  - Polymerase Chain Reaction
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-bcl-2
MH  - Signal Transduction
MH  - Stem Cells/drug effects/*physiology
MH  - Tretinoin/*pharmacology
PMC - PMC2120745
EDAT- 1996/03/01 00:00
MHDA- 1996/03/01 00:01
PMCR- 1996/09/01
CRDT- 1996/03/01 00:00
PHST- 1996/03/01 00:00 [pubmed]
PHST- 1996/03/01 00:01 [medline]
PHST- 1996/03/01 00:00 [entrez]
PHST- 1996/09/01 00:00 [pmc-release]
AID - 96180288 [pii]
AID - 10.1083/jcb.132.5.955 [doi]
PST - ppublish
SO  - J Cell Biol. 1996 Mar;132(5):955-68. doi: 10.1083/jcb.132.5.955.