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Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons

Programmed cell death is an ongoing process in both the developing and the mature nervous system. The tumor suppressor gene, p53, can induce apoptosis in a number of different cell types. Recently, the enhanced expression of p53 has been observed during acute neurological disease. To determine wheth...

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Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1996
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2133379/
https://www.ncbi.nlm.nih.gov/pubmed/8922388
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description Programmed cell death is an ongoing process in both the developing and the mature nervous system. The tumor suppressor gene, p53, can induce apoptosis in a number of different cell types. Recently, the enhanced expression of p53 has been observed during acute neurological disease. To determine whether p53 overexpression could influence neuronal survival, we used a recombinant adenovirus vector carrying wild type p53 to transduce postmitotic neurons. A control consisting of the same adenovirus vector background but carrying the lacZ reporter expression cassette was used to establish working parameters for the effective genetic manipulation of sympathetic neurons. We have found that recombinant adenovirus can be used at titers sufficiently high (10 to 50 multiplicity of infection) to transduce the majority of the neuronal population without perturbing survival, electrophysiological function, or cytoarchitecture. Moreover, we demonstrate that overexpression of wild type p53 is sufficient to induce programmed cell death in neurons. The observation that p53 is capable of inducing apoptosis in postmitotic neurons has major implications for the mechanisms of cell death in the traumatized mature nervous system.
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spelling pubmed-21333792008-05-01 Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons J Cell Biol Articles Programmed cell death is an ongoing process in both the developing and the mature nervous system. The tumor suppressor gene, p53, can induce apoptosis in a number of different cell types. Recently, the enhanced expression of p53 has been observed during acute neurological disease. To determine whether p53 overexpression could influence neuronal survival, we used a recombinant adenovirus vector carrying wild type p53 to transduce postmitotic neurons. A control consisting of the same adenovirus vector background but carrying the lacZ reporter expression cassette was used to establish working parameters for the effective genetic manipulation of sympathetic neurons. We have found that recombinant adenovirus can be used at titers sufficiently high (10 to 50 multiplicity of infection) to transduce the majority of the neuronal population without perturbing survival, electrophysiological function, or cytoarchitecture. Moreover, we demonstrate that overexpression of wild type p53 is sufficient to induce programmed cell death in neurons. The observation that p53 is capable of inducing apoptosis in postmitotic neurons has major implications for the mechanisms of cell death in the traumatized mature nervous system. The Rockefeller University Press 1996-11-02 /pmc/articles/PMC2133379/ /pubmed/8922388 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
Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons
title Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons
title_full Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons
title_fullStr Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons
title_full_unstemmed Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons
title_short Adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons
title_sort adenovirus-mediated gene transfer of the tumor suppressor, p53, induces apoptosis in postmitotic neurons
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2133379/
https://www.ncbi.nlm.nih.gov/pubmed/8922388