PMID: 8603926Mar 1, 1996Paper

Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells

The Journal of Cell Biology
H OkazawaI Kanazawa

Abstract

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 neurotr...Continue Reading

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Citations

Sep 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·L FalascaL Conti Devirgiliis
May 10, 2000·Neuroscience Research·K Yoshikawa
Jan 21, 2000·Brain Research. Molecular Brain Research·S TakeuchiH Okazawa
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Apr 29, 1998·Immunology and Cell Biology·L F Lincz
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Jul 18, 2006·Biochemical and Biophysical Research Communications·Joon Ho LeeYoung Han Lee
Nov 24, 2011·The International Journal of Biochemistry & Cell Biology·Chia-Hua LinYi-Rong Chen
Feb 3, 2005·Molecular Reproduction and Development·Peng WeiYi-Xun Liu
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Mar 26, 1998·Experimental Neurology·A T YachnisD K Anderson

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