Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels.

Several cell types express inducible nitric oxide synthase (NOS2) in response to exogenous insults such as bacterial lipopolysaccharide (LPS) or proinflammatory cytokines. For instance, muscular cells treated with LPS and interferon gamma (IFN-gamma) respond by increasing the mRNA and protein levels...

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Detalhes bibliográficos
Autores: Navarro-Lerida, Inmaculada, Portolés, María Teresa, Barrientos, Alberto Alvarez, Gavilanes, Francisco, Boscá, Lisardo, Rodriguez-Crespo, Ignacio
Tipo de documento: artigo
Data de publicação:2004
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositório:Repisalud
Idioma:inglês
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/11916
Acesso em linha:http://hdl.handle.net/20.500.12105/11916
Access Level:Acceso aberto
Palavra-chave:Down-Regulation
Amidines
Animals
Argininosuccinic Acid
Benzylamines
Caveolin 1
Caveolin 2
Caveolin 3
Caveolins
Cell Line
Enzyme Induction
Enzyme Inhibitors
Flavonoids
Interferon-gamma
Lipopolysaccharides
Mice
Mice, Knockout
Muscle Cells
Muscle Fibers, Skeletal
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitrites
Oligoribonucleotides, Antisense
Protein Binding
Protein Isoforms
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oai_identifier_str oai:repisalud.isciii.es:20.500.12105/11916
network_acronym_str ES
network_name_str España
repository_id_str
spelling Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels.Navarro-Lerida, InmaculadaPortolés, María TeresaBarrientos, Alberto AlvarezGavilanes, FranciscoBoscá, LisardoRodriguez-Crespo, IgnacioDown-RegulationAmidinesAnimalsArgininosuccinic AcidBenzylaminesCaveolin 1Caveolin 2Caveolin 3CaveolinsCell LineEnzyme InductionEnzyme InhibitorsFlavonoidsInterferon-gammaLipopolysaccharidesMiceMice, KnockoutMuscle CellsMuscle Fibers, SkeletalNitric Oxide SynthaseNitric Oxide Synthase Type IINitritesOligoribonucleotides, AntisenseProtein BindingProtein IsoformsSeveral cell types express inducible nitric oxide synthase (NOS2) in response to exogenous insults such as bacterial lipopolysaccharide (LPS) or proinflammatory cytokines. For instance, muscular cells treated with LPS and interferon gamma (IFN-gamma) respond by increasing the mRNA and protein levels of NOS2, and synthesize large amounts of nitric oxide. We show here that transcriptional induction of NOS2 in muscular cells proceeds with a concomitant decrease in the levels of caveolin-1, -2 and -3. Addition of *NO-releasing compounds to C2C12 muscle cells reveals that this downregulation of the caveolin (cav) levels is due to the presence of *NO itself in the case of caveolin-3 and to the action of the LPS/IFN-gamma in the case of cav-1 and cav-2. Likewise, muscle cells obtained from NOS2(-/-) knockout mice challenged with LPS/IFN-gamma could downregulate their levels of cav-1 but not of cav-3, unlike wild-type animals, in which both cav-1 and cav-3 levels diminished in the presence of the proinflammatory insult. Laser confocal immunofluorescence analysis proves that *NO exerts autocrine and paracrine actions, hence diminishing the cav-3 levels. When the induced NOS2 was purified using an affinity resin or immunoprecipitated from muscular tissues, it appears strongly bound not only to calmodulin but also to cav-1, and marginally to cav-2 and cav-3. When the cav levels where reduced using antisense oligonucleotides, an increase in the NOS2-derived.NO levels could be measured, demonstrating the inhibitory role of the three cav isoforms. Our results show that cells expressing NOS2 diminish their cav levels when the synthesis of *NO is required.The Company of Biologists20212021-02-1720042004-04-0120042004-04-01journal articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/11916reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/119162026-06-12T12:43:37Z
dc.title.none.fl_str_mv Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels.
title Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels.
spellingShingle Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels.
Navarro-Lerida, Inmaculada
Down-Regulation
Amidines
Animals
Argininosuccinic Acid
Benzylamines
Caveolin 1
Caveolin 2
Caveolin 3
Caveolins
Cell Line
Enzyme Induction
Enzyme Inhibitors
Flavonoids
Interferon-gamma
Lipopolysaccharides
Mice
Mice, Knockout
Muscle Cells
Muscle Fibers, Skeletal
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitrites
Oligoribonucleotides, Antisense
Protein Binding
Protein Isoforms
title_short Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels.
title_full Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels.
title_fullStr Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels.
title_full_unstemmed Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels.
title_sort Induction of nitric oxide synthase-2 proceeds with the concomitant downregulation of the endogenous caveolin levels.
dc.creator.none.fl_str_mv Navarro-Lerida, Inmaculada
Portolés, María Teresa
Barrientos, Alberto Alvarez
Gavilanes, Francisco
Boscá, Lisardo
Rodriguez-Crespo, Ignacio
author Navarro-Lerida, Inmaculada
author_facet Navarro-Lerida, Inmaculada
Portolés, María Teresa
Barrientos, Alberto Alvarez
Gavilanes, Francisco
Boscá, Lisardo
Rodriguez-Crespo, Ignacio
author_role author
author2 Portolés, María Teresa
Barrientos, Alberto Alvarez
Gavilanes, Francisco
Boscá, Lisardo
Rodriguez-Crespo, Ignacio
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Down-Regulation
Amidines
Animals
Argininosuccinic Acid
Benzylamines
Caveolin 1
Caveolin 2
Caveolin 3
Caveolins
Cell Line
Enzyme Induction
Enzyme Inhibitors
Flavonoids
Interferon-gamma
Lipopolysaccharides
Mice
Mice, Knockout
Muscle Cells
Muscle Fibers, Skeletal
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitrites
Oligoribonucleotides, Antisense
Protein Binding
Protein Isoforms
topic Down-Regulation
Amidines
Animals
Argininosuccinic Acid
Benzylamines
Caveolin 1
Caveolin 2
Caveolin 3
Caveolins
Cell Line
Enzyme Induction
Enzyme Inhibitors
Flavonoids
Interferon-gamma
Lipopolysaccharides
Mice
Mice, Knockout
Muscle Cells
Muscle Fibers, Skeletal
Nitric Oxide Synthase
Nitric Oxide Synthase Type II
Nitrites
Oligoribonucleotides, Antisense
Protein Binding
Protein Isoforms
description Several cell types express inducible nitric oxide synthase (NOS2) in response to exogenous insults such as bacterial lipopolysaccharide (LPS) or proinflammatory cytokines. For instance, muscular cells treated with LPS and interferon gamma (IFN-gamma) respond by increasing the mRNA and protein levels of NOS2, and synthesize large amounts of nitric oxide. We show here that transcriptional induction of NOS2 in muscular cells proceeds with a concomitant decrease in the levels of caveolin-1, -2 and -3. Addition of *NO-releasing compounds to C2C12 muscle cells reveals that this downregulation of the caveolin (cav) levels is due to the presence of *NO itself in the case of caveolin-3 and to the action of the LPS/IFN-gamma in the case of cav-1 and cav-2. Likewise, muscle cells obtained from NOS2(-/-) knockout mice challenged with LPS/IFN-gamma could downregulate their levels of cav-1 but not of cav-3, unlike wild-type animals, in which both cav-1 and cav-3 levels diminished in the presence of the proinflammatory insult. Laser confocal immunofluorescence analysis proves that *NO exerts autocrine and paracrine actions, hence diminishing the cav-3 levels. When the induced NOS2 was purified using an affinity resin or immunoprecipitated from muscular tissues, it appears strongly bound not only to calmodulin but also to cav-1, and marginally to cav-2 and cav-3. When the cav levels where reduced using antisense oligonucleotides, an increase in the NOS2-derived.NO levels could be measured, demonstrating the inhibitory role of the three cav isoforms. Our results show that cells expressing NOS2 diminish their cav levels when the synthesis of *NO is required.
publishDate 2004
dc.date.none.fl_str_mv 2004
2004-04-01
2004
2004-04-01
2021
2021-02-17
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/11916
url http://hdl.handle.net/20.500.12105/11916
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 The Company of Biologists
publisher.none.fl_str_mv The Company of Biologists
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869421516594085888
score 15.811543

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