Nitric oxide synthase isoforms and NF-jB activity in normal and osteoarthritic human chondrocytes: Regulation by inducible nitric oxide

Detalhes bibliográficos
Autor(a) principal: Rosa, Susana C.
Data de Publicação: 2008
Outros Autores: Judas, F., Lopes, M. C., Mendes, A. F.
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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spelling 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
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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
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dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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