Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells
Autor(a) principal: | |
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Data de Publicação: | 2012 |
Outros Autores: | , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.21/2618 |
Resumo: | Hyperhomocysteinemia (HHcy) is a risk factor for vascular disease, but the underlying mechanisms remain incompletely defined. Reduced bioavailability of nitric oxide (NO) is a principal manifestation of underlying endothelial dysfunction, which is an initial event in vascular disease. Inhibition of cellular methylation reactions by S-adenosylhomocysteine (AdoHcy), which accumulates during HHcy, has been suggested to contribute to vascular dysfunction. However, thus far, the effect of intracellular AdoHcy accumulation on NO bioavailability has not yet been fully substantiated by experimental evidence. The present study was carried out to evaluate whether disturbances in cellular methylation status affect NO production by cultured human endothelial cells. Here, we show that a hypomethylating environment, induced by the accumulation of AdoHcy, impairs NO production. Consistent with this finding, we observed decreased eNOS expression and activity, but, by contrast, enhanced NOS3 transcription. Taken together, our data support the existence of regulatory post-transcriptional mechanisms modulated by cellular methylation potential leading to impaired NO production by cultured human endothelial cells. As such, our conclusions may have implications for the HHcy-mediated reductions in NO bioavailability and endothelial dysfunction. |
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Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cellsNeurobiologyProteomicsLife sciencesBiochemical engineeringAnalytical chemistryBiochemistryHyperhomocysteinemia (HHcy) is a risk factor for vascular disease, but the underlying mechanisms remain incompletely defined. Reduced bioavailability of nitric oxide (NO) is a principal manifestation of underlying endothelial dysfunction, which is an initial event in vascular disease. Inhibition of cellular methylation reactions by S-adenosylhomocysteine (AdoHcy), which accumulates during HHcy, has been suggested to contribute to vascular dysfunction. However, thus far, the effect of intracellular AdoHcy accumulation on NO bioavailability has not yet been fully substantiated by experimental evidence. The present study was carried out to evaluate whether disturbances in cellular methylation status affect NO production by cultured human endothelial cells. Here, we show that a hypomethylating environment, induced by the accumulation of AdoHcy, impairs NO production. Consistent with this finding, we observed decreased eNOS expression and activity, but, by contrast, enhanced NOS3 transcription. Taken together, our data support the existence of regulatory post-transcriptional mechanisms modulated by cellular methylation potential leading to impaired NO production by cultured human endothelial cells. As such, our conclusions may have implications for the HHcy-mediated reductions in NO bioavailability and endothelial dysfunction.SpringerRCIPLBarroso, M.Rocha, M. S.Esse, R.Gonçalves, I. JrGomes, Anita Q.Teerlink, T.Jakobs, C.Blom, H. J.Loscalzo, J.Rivera, I.de Almeida, I. T.Castro, R.2013-08-21T13:49:28Z2012-052012-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.21/2618engBarroso M, Rocha MS, Esse R, Gonçalves I Jr, Gomes AQ, Teerlink T, et al. Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells. Amino Acids. 2012;42(5):1903-11.1438-2199info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-08-03T09:42:11Zoai:repositorio.ipl.pt:10400.21/2618Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:12:22.379333Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells |
title |
Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells |
spellingShingle |
Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells Barroso, M. Neurobiology Proteomics Life sciences Biochemical engineering Analytical chemistry Biochemistry |
title_short |
Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells |
title_full |
Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells |
title_fullStr |
Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells |
title_full_unstemmed |
Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells |
title_sort |
Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells |
author |
Barroso, M. |
author_facet |
Barroso, M. Rocha, M. S. Esse, R. Gonçalves, I. Jr Gomes, Anita Q. Teerlink, T. Jakobs, C. Blom, H. J. Loscalzo, J. Rivera, I. de Almeida, I. T. Castro, R. |
author_role |
author |
author2 |
Rocha, M. S. Esse, R. Gonçalves, I. Jr Gomes, Anita Q. Teerlink, T. Jakobs, C. Blom, H. J. Loscalzo, J. Rivera, I. de Almeida, I. T. Castro, R. |
author2_role |
author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
RCIPL |
dc.contributor.author.fl_str_mv |
Barroso, M. Rocha, M. S. Esse, R. Gonçalves, I. Jr Gomes, Anita Q. Teerlink, T. Jakobs, C. Blom, H. J. Loscalzo, J. Rivera, I. de Almeida, I. T. Castro, R. |
dc.subject.por.fl_str_mv |
Neurobiology Proteomics Life sciences Biochemical engineering Analytical chemistry Biochemistry |
topic |
Neurobiology Proteomics Life sciences Biochemical engineering Analytical chemistry Biochemistry |
description |
Hyperhomocysteinemia (HHcy) is a risk factor for vascular disease, but the underlying mechanisms remain incompletely defined. Reduced bioavailability of nitric oxide (NO) is a principal manifestation of underlying endothelial dysfunction, which is an initial event in vascular disease. Inhibition of cellular methylation reactions by S-adenosylhomocysteine (AdoHcy), which accumulates during HHcy, has been suggested to contribute to vascular dysfunction. However, thus far, the effect of intracellular AdoHcy accumulation on NO bioavailability has not yet been fully substantiated by experimental evidence. The present study was carried out to evaluate whether disturbances in cellular methylation status affect NO production by cultured human endothelial cells. Here, we show that a hypomethylating environment, induced by the accumulation of AdoHcy, impairs NO production. Consistent with this finding, we observed decreased eNOS expression and activity, but, by contrast, enhanced NOS3 transcription. Taken together, our data support the existence of regulatory post-transcriptional mechanisms modulated by cellular methylation potential leading to impaired NO production by cultured human endothelial cells. As such, our conclusions may have implications for the HHcy-mediated reductions in NO bioavailability and endothelial dysfunction. |
publishDate |
2012 |
dc.date.none.fl_str_mv |
2012-05 2012-05-01T00:00:00Z 2013-08-21T13:49:28Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.21/2618 |
url |
http://hdl.handle.net/10400.21/2618 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Barroso M, Rocha MS, Esse R, Gonçalves I Jr, Gomes AQ, Teerlink T, et al. Cellular hypomethylation is associated with impaired nitric oxide production by cultured human endothelial cells. Amino Acids. 2012;42(5):1903-11. 1438-2199 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Springer |
publisher.none.fl_str_mv |
Springer |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133378577956864 |