Cargando…

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

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 fragmenta...

Descripción completa

Detalles Bibliográficos
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1996
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2120745/
https://www.ncbi.nlm.nih.gov/pubmed/8603926
_version_ 1782141567550619648
collection PubMed
description 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.
format Text
id pubmed-2120745
institution National Center for Biotechnology Information
language English
publishDate 1996
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21207452008-05-01 Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells J Cell Biol Articles 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. The Rockefeller University Press 1996-03-01 /pmc/articles/PMC2120745/ /pubmed/8603926 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells
title Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells
title_full Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells
title_fullStr Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells
title_full_unstemmed Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells
title_short Bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells
title_sort bcl-2 inhibits retinoic acid-induced apoptosis during the neural differentiation of embryonal stem cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2120745/
https://www.ncbi.nlm.nih.gov/pubmed/8603926