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Inhibition of Apoptotic Signaling Cascades Causes Loss of Trophic Factor Dependence during Neuronal Maturation

During development, neurons are acutely dependent on target-derived trophic factors for survival. This dependence on trophic support decreases dramatically with maturation in several neuronal populations, including sympathetic neurons. Analyses of nerve growth factor deprivation in immature and matu...

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Autores principales: Putcha, Girish V., Deshmukh, Mohanish, Johnson, Eugene M.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2000
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174821/
https://www.ncbi.nlm.nih.gov/pubmed/10831605
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author Putcha, Girish V.
Deshmukh, Mohanish
Johnson, Eugene M.
author_facet Putcha, Girish V.
Deshmukh, Mohanish
Johnson, Eugene M.
author_sort Putcha, Girish V.
collection PubMed
description During development, neurons are acutely dependent on target-derived trophic factors for survival. This dependence on trophic support decreases dramatically with maturation in several neuronal populations, including sympathetic neurons. Analyses of nerve growth factor deprivation in immature and mature sympathetic neurons indicate that maturation aborts the cell death pathway at a point that is mechanistically indistinguishable from Bax deletion. However, neither the mRNA nor protein level of BAX changes with neuronal maturation. Therefore, BAX must be regulated posttranslationally in mature neurons. Nerve growth factor deprivation in immature sympathetic neurons induces two parallel processes: (a) a protein synthesis–dependent, caspase-independent translocation of BAX from the cytosol to mitochondria, followed by mitochondrial membrane integration and loss of cytochrome c; and (b) the development of competence-to-die, which requires neither macromolecular synthesis nor BAX expression. Activation of both signaling pathways is required for caspase activation and apoptosis in immature sympathetic neurons. In contrast, nerve growth factor withdrawal in mature sympathetic neurons did not induce the translocation of either BAX or cytochrome c. Moreover, mature neurons did not develop competence-to-die with cytoplasmic accumulation of cytochrome c. Therefore, inhibition of both BAX-dependent cytochrome c release and the development of competence-to-die contributed to the loss of trophic factor dependence associated with neuronal maturation.
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spelling pubmed-21748212008-05-01 Inhibition of Apoptotic Signaling Cascades Causes Loss of Trophic Factor Dependence during Neuronal Maturation Putcha, Girish V. Deshmukh, Mohanish Johnson, Eugene M. J Cell Biol Brief Report During development, neurons are acutely dependent on target-derived trophic factors for survival. This dependence on trophic support decreases dramatically with maturation in several neuronal populations, including sympathetic neurons. Analyses of nerve growth factor deprivation in immature and mature sympathetic neurons indicate that maturation aborts the cell death pathway at a point that is mechanistically indistinguishable from Bax deletion. However, neither the mRNA nor protein level of BAX changes with neuronal maturation. Therefore, BAX must be regulated posttranslationally in mature neurons. Nerve growth factor deprivation in immature sympathetic neurons induces two parallel processes: (a) a protein synthesis–dependent, caspase-independent translocation of BAX from the cytosol to mitochondria, followed by mitochondrial membrane integration and loss of cytochrome c; and (b) the development of competence-to-die, which requires neither macromolecular synthesis nor BAX expression. Activation of both signaling pathways is required for caspase activation and apoptosis in immature sympathetic neurons. In contrast, nerve growth factor withdrawal in mature sympathetic neurons did not induce the translocation of either BAX or cytochrome c. Moreover, mature neurons did not develop competence-to-die with cytoplasmic accumulation of cytochrome c. Therefore, inhibition of both BAX-dependent cytochrome c release and the development of competence-to-die contributed to the loss of trophic factor dependence associated with neuronal maturation. The Rockefeller University Press 2000-05-29 /pmc/articles/PMC2174821/ /pubmed/10831605 Text en © 2000 The Rockefeller University Press 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 Brief Report
Putcha, Girish V.
Deshmukh, Mohanish
Johnson, Eugene M.
Inhibition of Apoptotic Signaling Cascades Causes Loss of Trophic Factor Dependence during Neuronal Maturation
title Inhibition of Apoptotic Signaling Cascades Causes Loss of Trophic Factor Dependence during Neuronal Maturation
title_full Inhibition of Apoptotic Signaling Cascades Causes Loss of Trophic Factor Dependence during Neuronal Maturation
title_fullStr Inhibition of Apoptotic Signaling Cascades Causes Loss of Trophic Factor Dependence during Neuronal Maturation
title_full_unstemmed Inhibition of Apoptotic Signaling Cascades Causes Loss of Trophic Factor Dependence during Neuronal Maturation
title_short Inhibition of Apoptotic Signaling Cascades Causes Loss of Trophic Factor Dependence during Neuronal Maturation
title_sort inhibition of apoptotic signaling cascades causes loss of trophic factor dependence during neuronal maturation
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2174821/
https://www.ncbi.nlm.nih.gov/pubmed/10831605
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