p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats

An association of increased apoptosis with overexpression of the proapoptotic protein Bax-alpha has been reported in the left ventricle of adult spontaneously hypertensive rats (SHR). Both alterations were corrected in SHR that received long-term treatment with the AT1 antagonist losartan. To gain i...

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Autores: Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec, Zalba-Goñi, G. (Guillermo)|||/items/71410fa2-baa5-4efc-bce7-14b4b0e23802, Ravassa-Albéniz, S. (Susana)|||/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1, Elom, E. (E.) De|||/items/a8a8185b-2f22-4390-8107-81435c96ebc9, Beaumont-Ezcurra, F.J. (Francisco Javier)|||/items/6824d098-1970-4668-9169-8f1f3352e015, Fortuño, A. (Ana)|||/items/2324831f-71b3-4d1b-afc1-594e4e1bc0c9, Diez-Martinez, J. (Javier)|||/items/4f3a0e43-12bf-403d-9dc7-31fab0d11d41
Tipo de recurso: artículo
Fecha de publicación:1999
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/19881
Acceso en línea:https://hdl.handle.net/10171/19881
Access Level:acceso abierto
Palabra clave:Apoptosis
BAX gene
Protein, Bax-a
Ventricular function, left
P53
Rats, inbred SHR
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spelling p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive ratsFortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ecZalba-Goñi, G. (Guillermo)|||/items/71410fa2-baa5-4efc-bce7-14b4b0e23802Ravassa-Albéniz, S. (Susana)|||/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1Elom, E. (E.) De|||/items/a8a8185b-2f22-4390-8107-81435c96ebc9Beaumont-Ezcurra, F.J. (Francisco Javier)|||/items/6824d098-1970-4668-9169-8f1f3352e015Fortuño, A. (Ana)|||/items/2324831f-71b3-4d1b-afc1-594e4e1bc0c9Diez-Martinez, J. (Javier)|||/items/4f3a0e43-12bf-403d-9dc7-31fab0d11d41ApoptosisBAX geneProtein, Bax-aVentricular function, leftP53Rats, inbred SHRAn association of increased apoptosis with overexpression of the proapoptotic protein Bax-alpha has been reported in the left ventricle of adult spontaneously hypertensive rats (SHR). Both alterations were corrected in SHR that received long-term treatment with the AT1 antagonist losartan. To gain insight into the regulation of cardiac Bax-alpha protein in genetic hypertension, we investigated the expression of the protein p53 (a BAX gene transcription factor) and BAX mRNA in the left ventricle of 30-week-old Wistar-Kyoto rats (WKY), SHR, and SHR treated with losartan (20 mg. kg-1. d-1) during 14 weeks before death. The expression of p53 and Bax proteins was assessed by Western blot analysis. The expression of BAX mRNA was assessed by Northern blot analysis. The density of apoptotic cells was assessed by direct immunoperoxidase detection of biotin-labeled deoxyuridine nucleotides. Compared with WKY, untreated SHR exhibited increased apoptosis (P<0.05), increased Bax-alpha protein (P<0.05), and similar levels of p53 protein and BAX mRNA. Losartan given long term was associated with the normalization of apoptosis and Bax-alpha protein expression. The expression of BAX mRNA was decreased (P<0. 05) in treated SHR compared with untreated SHR. No changes in the expression of p53 protein were observed in losartan-treated SHR. These results suggest that overexpression of the Bax-alpha protein seen in the left ventricle of adult SHR with increased apoptosis is not related to a p53-mediated upregulation of BAX gene transcription. Our data also suggest that normalization of Bax-alpha protein observed in SHR after long-term blockade of angiotensin II type 1 receptors may be due to the inhibition of BAX gene transcription.American Heart AssociationDadun. Depósito Académico Digital Universidad de Navarra20112011-11-1819991999-01-0119991999-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/19881reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/198812026-06-21T12:47:57Z
dc.title.none.fl_str_mv p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats
title p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats
spellingShingle p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats
Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
Apoptosis
BAX gene
Protein, Bax-a
Ventricular function, left
P53
Rats, inbred SHR
title_short p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats
title_full p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats
title_fullStr p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats
title_full_unstemmed p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats
title_sort p53-mediated upregulation of BAX gene transcription is not involved in Bax-alpha protein overexpression in the left ventricle of spontaneously hypertensive rats
dc.creator.none.fl_str_mv Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
Zalba-Goñi, G. (Guillermo)|||/items/71410fa2-baa5-4efc-bce7-14b4b0e23802
Ravassa-Albéniz, S. (Susana)|||/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1
Elom, E. (E.) De|||/items/a8a8185b-2f22-4390-8107-81435c96ebc9
Beaumont-Ezcurra, F.J. (Francisco Javier)|||/items/6824d098-1970-4668-9169-8f1f3352e015
Fortuño, A. (Ana)|||/items/2324831f-71b3-4d1b-afc1-594e4e1bc0c9
Diez-Martinez, J. (Javier)|||/items/4f3a0e43-12bf-403d-9dc7-31fab0d11d41
author Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
author_facet Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
Zalba-Goñi, G. (Guillermo)|||/items/71410fa2-baa5-4efc-bce7-14b4b0e23802
Ravassa-Albéniz, S. (Susana)|||/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1
Elom, E. (E.) De|||/items/a8a8185b-2f22-4390-8107-81435c96ebc9
Beaumont-Ezcurra, F.J. (Francisco Javier)|||/items/6824d098-1970-4668-9169-8f1f3352e015
Fortuño, A. (Ana)|||/items/2324831f-71b3-4d1b-afc1-594e4e1bc0c9
Diez-Martinez, J. (Javier)|||/items/4f3a0e43-12bf-403d-9dc7-31fab0d11d41
author_role author
author2 Zalba-Goñi, G. (Guillermo)|||/items/71410fa2-baa5-4efc-bce7-14b4b0e23802
Ravassa-Albéniz, S. (Susana)|||/items/df0c1eb3-9f45-4d77-a7a5-aca2bcf425e1
Elom, E. (E.) De|||/items/a8a8185b-2f22-4390-8107-81435c96ebc9
Beaumont-Ezcurra, F.J. (Francisco Javier)|||/items/6824d098-1970-4668-9169-8f1f3352e015
Fortuño, A. (Ana)|||/items/2324831f-71b3-4d1b-afc1-594e4e1bc0c9
Diez-Martinez, J. (Javier)|||/items/4f3a0e43-12bf-403d-9dc7-31fab0d11d41
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Apoptosis
BAX gene
Protein, Bax-a
Ventricular function, left
P53
Rats, inbred SHR
topic Apoptosis
BAX gene
Protein, Bax-a
Ventricular function, left
P53
Rats, inbred SHR
description An association of increased apoptosis with overexpression of the proapoptotic protein Bax-alpha has been reported in the left ventricle of adult spontaneously hypertensive rats (SHR). Both alterations were corrected in SHR that received long-term treatment with the AT1 antagonist losartan. To gain insight into the regulation of cardiac Bax-alpha protein in genetic hypertension, we investigated the expression of the protein p53 (a BAX gene transcription factor) and BAX mRNA in the left ventricle of 30-week-old Wistar-Kyoto rats (WKY), SHR, and SHR treated with losartan (20 mg. kg-1. d-1) during 14 weeks before death. The expression of p53 and Bax proteins was assessed by Western blot analysis. The expression of BAX mRNA was assessed by Northern blot analysis. The density of apoptotic cells was assessed by direct immunoperoxidase detection of biotin-labeled deoxyuridine nucleotides. Compared with WKY, untreated SHR exhibited increased apoptosis (P<0.05), increased Bax-alpha protein (P<0.05), and similar levels of p53 protein and BAX mRNA. Losartan given long term was associated with the normalization of apoptosis and Bax-alpha protein expression. The expression of BAX mRNA was decreased (P<0. 05) in treated SHR compared with untreated SHR. No changes in the expression of p53 protein were observed in losartan-treated SHR. These results suggest that overexpression of the Bax-alpha protein seen in the left ventricle of adult SHR with increased apoptosis is not related to a p53-mediated upregulation of BAX gene transcription. Our data also suggest that normalization of Bax-alpha protein observed in SHR after long-term blockade of angiotensin II type 1 receptors may be due to the inhibition of BAX gene transcription.
publishDate 1999
dc.date.none.fl_str_mv 1999
1999-01-01
1999
1999-01-01
2011
2011-11-18
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/19881
url https://hdl.handle.net/10171/19881
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv American Heart Association
publisher.none.fl_str_mv American Heart Association
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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