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Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis
Heme oxygenase 1 (HO-1) inhibits apoptosis by regulating cellular prooxidant iron. We now show that there is an additional mechanism by which HO-1 inhibits apoptosis, namely by generating the gaseous molecule carbon monoxide (CO). Overexpression of HO-1, or induction of HO-1 expression by heme, prot...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2000
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193315/ https://www.ncbi.nlm.nih.gov/pubmed/11015442 |
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author | Brouard, Sophie Otterbein, Leo E. Anrather, Josef Tobiasch, Edda Bach, Fritz H. Choi, Augustine M.K. Soares, Miguel P. |
author_facet | Brouard, Sophie Otterbein, Leo E. Anrather, Josef Tobiasch, Edda Bach, Fritz H. Choi, Augustine M.K. Soares, Miguel P. |
author_sort | Brouard, Sophie |
collection | PubMed |
description | Heme oxygenase 1 (HO-1) inhibits apoptosis by regulating cellular prooxidant iron. We now show that there is an additional mechanism by which HO-1 inhibits apoptosis, namely by generating the gaseous molecule carbon monoxide (CO). Overexpression of HO-1, or induction of HO-1 expression by heme, protects endothelial cells (ECs) from apoptosis. When HO-1 enzymatic activity is blocked by tin protoporphyrin (SnPPIX) or the action of CO is inhibited by hemoglobin (Hb), HO-1 no longer prevents EC apoptosis while these reagents do not affect the antiapoptotic action of bcl-2. Exposure of ECs to exogenous CO, under inhibition of HO-1 activity by SnPPIX, substitutes HO-1 in preventing EC apoptosis. The mechanism of action of HO-1/CO is dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) signaling transduction pathway. Expression of HO-1 or exposure of ECs to exogenous CO enhanced p38 MAPK activation by TNF-α. Specific inhibition of p38 MAPK activation by the pyridinyl imidazol SB203580 or through overexpression of a p38 MAPK dominant negative mutant abrogated the antiapoptotic effect of HO-1. Taken together, these data demonstrate that the antiapoptotic effect of HO-1 in ECs is mediated by CO and more specifically via the activation of p38 MAPK by CO. |
format | Text |
id | pubmed-2193315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2000 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21933152008-04-16 Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis Brouard, Sophie Otterbein, Leo E. Anrather, Josef Tobiasch, Edda Bach, Fritz H. Choi, Augustine M.K. Soares, Miguel P. J Exp Med Original Article Heme oxygenase 1 (HO-1) inhibits apoptosis by regulating cellular prooxidant iron. We now show that there is an additional mechanism by which HO-1 inhibits apoptosis, namely by generating the gaseous molecule carbon monoxide (CO). Overexpression of HO-1, or induction of HO-1 expression by heme, protects endothelial cells (ECs) from apoptosis. When HO-1 enzymatic activity is blocked by tin protoporphyrin (SnPPIX) or the action of CO is inhibited by hemoglobin (Hb), HO-1 no longer prevents EC apoptosis while these reagents do not affect the antiapoptotic action of bcl-2. Exposure of ECs to exogenous CO, under inhibition of HO-1 activity by SnPPIX, substitutes HO-1 in preventing EC apoptosis. The mechanism of action of HO-1/CO is dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) signaling transduction pathway. Expression of HO-1 or exposure of ECs to exogenous CO enhanced p38 MAPK activation by TNF-α. Specific inhibition of p38 MAPK activation by the pyridinyl imidazol SB203580 or through overexpression of a p38 MAPK dominant negative mutant abrogated the antiapoptotic effect of HO-1. Taken together, these data demonstrate that the antiapoptotic effect of HO-1 in ECs is mediated by CO and more specifically via the activation of p38 MAPK by CO. The Rockefeller University Press 2000-10-02 /pmc/articles/PMC2193315/ /pubmed/11015442 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 | Original Article Brouard, Sophie Otterbein, Leo E. Anrather, Josef Tobiasch, Edda Bach, Fritz H. Choi, Augustine M.K. Soares, Miguel P. Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis |
title | Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis |
title_full | Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis |
title_fullStr | Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis |
title_full_unstemmed | Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis |
title_short | Carbon Monoxide Generated by Heme Oxygenase 1 Suppresses Endothelial Cell Apoptosis |
title_sort | carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193315/ https://www.ncbi.nlm.nih.gov/pubmed/11015442 |
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