Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxide
Autor(a) principal: | |
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Data de Publicação: | 2008 |
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/10316/11790 https://doi.org/10.1016/j.niox.2008.07.005 |
Resumo: | To elucidate the role of endogenous inducible nitric oxide (NO) on the regulation of NF-jB activity in human chondrocytes, we evaluated (i) the pattern of expression of the neuronal (nNOS) and inducible (iNOS) NO synthase isoforms and the basal NF-jB activity in normal and osteoarthritic (OA) human chondrocytes, (ii) the role of cytokines and growth factors in modulating the protein levels of the two NOS isoforms, and (iii) the effect of inhibiting endogenous inducible NO production on the ability of interleukin- 1b (IL-1) to induce NF-jB activation. nNOS was more frequently expressed in normal than in OA chondrocytes, whereas the opposite was found for iNOS. IL-1 induced the degradation of both enzymes, but iNOS disappeared more rapidly. Although IjB-a was present in all the normal samples and in the majority of the OA samples, NF-jB–DNA binding activity in OA chondrocytes was increased approximately twofold relatively to normal cells. Addition of a NOS inhibitor, after induction of iNOS expression, induced IjB-a degradation and potenciated the effect of IL-1, indicating that endogenous inducible NO inhibits NF-jB activation. Taken together, these findings favor an inhibitory role of high NO levels on the regulation of NF-jB activation in chondrocytes, indicating that NF-jB activity is regulated, at least in part, by the balanced production of NO resulting from a dynamic process that, at any given moment, determines the availability of the constitutive and inducible NOS isoforms. Moreover, the down-regulatory role of NO on NF-jB activation warrants caution as to the possible utilization of NO inhibitors in the therapy of OA. |
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Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxideCondrócitosInterleucina 1-bNF-jBÓxido nítricoOsteoartriteDegradação das proteínasSintase do óxido nítrico neuronalSintase do óxido nítrico indusívelTo elucidate the role of endogenous inducible nitric oxide (NO) on the regulation of NF-jB activity in human chondrocytes, we evaluated (i) the pattern of expression of the neuronal (nNOS) and inducible (iNOS) NO synthase isoforms and the basal NF-jB activity in normal and osteoarthritic (OA) human chondrocytes, (ii) the role of cytokines and growth factors in modulating the protein levels of the two NOS isoforms, and (iii) the effect of inhibiting endogenous inducible NO production on the ability of interleukin- 1b (IL-1) to induce NF-jB activation. nNOS was more frequently expressed in normal than in OA chondrocytes, whereas the opposite was found for iNOS. IL-1 induced the degradation of both enzymes, but iNOS disappeared more rapidly. Although IjB-a was present in all the normal samples and in the majority of the OA samples, NF-jB–DNA binding activity in OA chondrocytes was increased approximately twofold relatively to normal cells. Addition of a NOS inhibitor, after induction of iNOS expression, induced IjB-a degradation and potenciated the effect of IL-1, indicating that endogenous inducible NO inhibits NF-jB activation. Taken together, these findings favor an inhibitory role of high NO levels on the regulation of NF-jB activation in chondrocytes, indicating that NF-jB activity is regulated, at least in part, by the balanced production of NO resulting from a dynamic process that, at any given moment, determines the availability of the constitutive and inducible NOS isoforms. Moreover, the down-regulatory role of NO on NF-jB activation warrants caution as to the possible utilization of NO inhibitors in the therapy of OA.a Center for Neurosciences and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal b Faculty of Pharmacy, University of Coimbra, 3000-295 Coimbra, Portugal c Orthopedics Department, University Hospital of Coimbra, Coimbra, Portugal d Faculty of Medicine, University of Coimbra, Coimbra, Portugal www.elsevier.com/ locate/ynioxElsevier2008-07-17info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/11790http://hdl.handle.net/10316/11790https://doi.org/10.1016/j.niox.2008.07.005engNitric Oxide. 19 (2008) 276–283Rosa, Susana C.Judas, F.Lopes, M. C.Mendes, A. F.info: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:RCAAP2022-05-25T03:16:45Zoai:estudogeral.uc.pt:10316/11790Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T20:47:25.179807Repositório 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 |
Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxide |
title |
Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxide |
spellingShingle |
Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxide Rosa, Susana C. Condrócitos Interleucina 1-b NF-jB Óxido nítrico Osteoartrite Degradação das proteínas Sintase do óxido nítrico neuronal Sintase do óxido nítrico indusível |
title_short |
Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxide |
title_full |
Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxide |
title_fullStr |
Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxide |
title_full_unstemmed |
Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxide |
title_sort |
Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxide |
author |
Rosa, Susana C. |
author_facet |
Rosa, Susana C. Judas, F. Lopes, M. C. Mendes, A. F. |
author_role |
author |
author2 |
Judas, F. Lopes, M. C. Mendes, A. F. |
author2_role |
author author author |
dc.contributor.author.fl_str_mv |
Rosa, Susana C. Judas, F. Lopes, M. C. Mendes, A. F. |
dc.subject.por.fl_str_mv |
Condrócitos Interleucina 1-b NF-jB Óxido nítrico Osteoartrite Degradação das proteínas Sintase do óxido nítrico neuronal Sintase do óxido nítrico indusível |
topic |
Condrócitos Interleucina 1-b NF-jB Óxido nítrico Osteoartrite Degradação das proteínas Sintase do óxido nítrico neuronal Sintase do óxido nítrico indusível |
description |
To elucidate the role of endogenous inducible nitric oxide (NO) on the regulation of NF-jB activity in human chondrocytes, we evaluated (i) the pattern of expression of the neuronal (nNOS) and inducible (iNOS) NO synthase isoforms and the basal NF-jB activity in normal and osteoarthritic (OA) human chondrocytes, (ii) the role of cytokines and growth factors in modulating the protein levels of the two NOS isoforms, and (iii) the effect of inhibiting endogenous inducible NO production on the ability of interleukin- 1b (IL-1) to induce NF-jB activation. nNOS was more frequently expressed in normal than in OA chondrocytes, whereas the opposite was found for iNOS. IL-1 induced the degradation of both enzymes, but iNOS disappeared more rapidly. Although IjB-a was present in all the normal samples and in the majority of the OA samples, NF-jB–DNA binding activity in OA chondrocytes was increased approximately twofold relatively to normal cells. Addition of a NOS inhibitor, after induction of iNOS expression, induced IjB-a degradation and potenciated the effect of IL-1, indicating that endogenous inducible NO inhibits NF-jB activation. Taken together, these findings favor an inhibitory role of high NO levels on the regulation of NF-jB activation in chondrocytes, indicating that NF-jB activity is regulated, at least in part, by the balanced production of NO resulting from a dynamic process that, at any given moment, determines the availability of the constitutive and inducible NOS isoforms. Moreover, the down-regulatory role of NO on NF-jB activation warrants caution as to the possible utilization of NO inhibitors in the therapy of OA. |
publishDate |
2008 |
dc.date.none.fl_str_mv |
2008-07-17 |
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/10316/11790 http://hdl.handle.net/10316/11790 https://doi.org/10.1016/j.niox.2008.07.005 |
url |
http://hdl.handle.net/10316/11790 https://doi.org/10.1016/j.niox.2008.07.005 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Nitric Oxide. 19 (2008) 276–283 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Elsevier |
publisher.none.fl_str_mv |
Elsevier |
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 |
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RCAAP |
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RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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