Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization

Autores
Chaudhuri, Pinaki; Rosenbaum, Michael A.; Birnbaumer, Lutz; Graham, Linda M.
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels, and the subsequent increase in intracellular Ca2+ leads to TRPC5 activation. The goal of this study is to elucidate the steps in the pathway between TRPC6 activation and TRPC5 externalization. Following TRPC6 activation by lysoPC, extracellular regulated kinase (ERK) is phosphorylated. This leads to phosphorylation of p47phox and subsequent NADPH oxidase activation with increased production of reactive oxygen species. ERK activation requires TRPC6 opening and influx of Ca2+ as evidenced by the failure of lysoPC to induce ERK phosphorylation in TRPC6−/− endothelial cells. ERK siRNA blocks the lysoPC-induced activation of NADPH oxidase, demonstrating that ERK activation is upstream of NADPH oxidase. The reactive oxygen species produced by NADPH oxidase promote myosin light chain kinase (MLCK) activation with phosphorylation of MLC and TRPC5 externalization. Downregulation of ERK, NADPH oxidase, or MLCK with the relevant siRNA prevents TRPC5 externalization. Blocking MLCK activation prevents the prolonged rise in intracellular calcium levels and preserves endothelial migration in the presence of lysoPC.
Fil: Chaudhuri, Pinaki. Cleveland Clinic; Estados Unidos
Fil: Rosenbaum, Michael A.. Cleveland Clinic; Estados Unidos. Louis Stokes Cleveland Veterans Affairs Medical Center; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Research Triangle Park; Estados Unidos. Cleveland Clinic; Estados Unidos
Fil: Graham, Linda M.. Cleveland Clinic; Estados Unidos
Materia
Trpc6
Trpc5
Nadph
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/48812
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/48812
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalizationChaudhuri, PinakiRosenbaum, Michael A.Birnbaumer, LutzGraham, Linda M.Trpc6Trpc5Nadphhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels, and the subsequent increase in intracellular Ca2+ leads to TRPC5 activation. The goal of this study is to elucidate the steps in the pathway between TRPC6 activation and TRPC5 externalization. Following TRPC6 activation by lysoPC, extracellular regulated kinase (ERK) is phosphorylated. This leads to phosphorylation of p47phox and subsequent NADPH oxidase activation with increased production of reactive oxygen species. ERK activation requires TRPC6 opening and influx of Ca2+ as evidenced by the failure of lysoPC to induce ERK phosphorylation in TRPC6−/− endothelial cells. ERK siRNA blocks the lysoPC-induced activation of NADPH oxidase, demonstrating that ERK activation is upstream of NADPH oxidase. The reactive oxygen species produced by NADPH oxidase promote myosin light chain kinase (MLCK) activation with phosphorylation of MLC and TRPC5 externalization. Downregulation of ERK, NADPH oxidase, or MLCK with the relevant siRNA prevents TRPC5 externalization. Blocking MLCK activation prevents the prolonged rise in intracellular calcium levels and preserves endothelial migration in the presence of lysoPC.Fil: Chaudhuri, Pinaki. Cleveland Clinic; Estados UnidosFil: Rosenbaum, Michael A.. Cleveland Clinic; Estados Unidos. Louis Stokes Cleveland Veterans Affairs Medical Center; Estados UnidosFil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Research Triangle Park; Estados Unidos. Cleveland Clinic; Estados UnidosFil: Graham, Linda M.. Cleveland Clinic; Estados UnidosAmerican Physiological Society2017-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/48812Chaudhuri, Pinaki; Rosenbaum, Michael A.; Birnbaumer, Lutz; Graham, Linda M.; Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization; American Physiological Society; American Journal of Physiology-cell Physiology; 313; 5; 11-2017; 541-5550363-6143CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/10.1152/ajpcell.00028.2017info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpcell.00028.2017info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:47:55Zoai:ri.conicet.gov.ar:11336/48812instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:47:56.194CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
title Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
spellingShingle Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
Chaudhuri, Pinaki
Trpc6
Trpc5
Nadph
title_short Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
title_full Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
title_fullStr Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
title_full_unstemmed Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
title_sort Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization
dc.creator.none.fl_str_mv Chaudhuri, Pinaki
Rosenbaum, Michael A.
Birnbaumer, Lutz
Graham, Linda M.
author Chaudhuri, Pinaki
author_facet Chaudhuri, Pinaki
Rosenbaum, Michael A.
Birnbaumer, Lutz
Graham, Linda M.
author_role author
author2 Rosenbaum, Michael A.
Birnbaumer, Lutz
Graham, Linda M.
author2_role author
author
author
dc.subject.none.fl_str_mv Trpc6
Trpc5
Nadph
topic Trpc6
Trpc5
Nadph
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels, and the subsequent increase in intracellular Ca2+ leads to TRPC5 activation. The goal of this study is to elucidate the steps in the pathway between TRPC6 activation and TRPC5 externalization. Following TRPC6 activation by lysoPC, extracellular regulated kinase (ERK) is phosphorylated. This leads to phosphorylation of p47phox and subsequent NADPH oxidase activation with increased production of reactive oxygen species. ERK activation requires TRPC6 opening and influx of Ca2+ as evidenced by the failure of lysoPC to induce ERK phosphorylation in TRPC6−/− endothelial cells. ERK siRNA blocks the lysoPC-induced activation of NADPH oxidase, demonstrating that ERK activation is upstream of NADPH oxidase. The reactive oxygen species produced by NADPH oxidase promote myosin light chain kinase (MLCK) activation with phosphorylation of MLC and TRPC5 externalization. Downregulation of ERK, NADPH oxidase, or MLCK with the relevant siRNA prevents TRPC5 externalization. Blocking MLCK activation prevents the prolonged rise in intracellular calcium levels and preserves endothelial migration in the presence of lysoPC.
Fil: Chaudhuri, Pinaki. Cleveland Clinic; Estados Unidos
Fil: Rosenbaum, Michael A.. Cleveland Clinic; Estados Unidos. Louis Stokes Cleveland Veterans Affairs Medical Center; Estados Unidos
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina. Research Triangle Park; Estados Unidos. Cleveland Clinic; Estados Unidos
Fil: Graham, Linda M.. Cleveland Clinic; Estados Unidos
description Lipid oxidation products, including lysophosphatidylcholine (lysoPC), activate canonical transient receptor potential 6 (TRPC6) channels, and the subsequent increase in intracellular Ca2+ leads to TRPC5 activation. The goal of this study is to elucidate the steps in the pathway between TRPC6 activation and TRPC5 externalization. Following TRPC6 activation by lysoPC, extracellular regulated kinase (ERK) is phosphorylated. This leads to phosphorylation of p47phox and subsequent NADPH oxidase activation with increased production of reactive oxygen species. ERK activation requires TRPC6 opening and influx of Ca2+ as evidenced by the failure of lysoPC to induce ERK phosphorylation in TRPC6−/− endothelial cells. ERK siRNA blocks the lysoPC-induced activation of NADPH oxidase, demonstrating that ERK activation is upstream of NADPH oxidase. The reactive oxygen species produced by NADPH oxidase promote myosin light chain kinase (MLCK) activation with phosphorylation of MLC and TRPC5 externalization. Downregulation of ERK, NADPH oxidase, or MLCK with the relevant siRNA prevents TRPC5 externalization. Blocking MLCK activation prevents the prolonged rise in intracellular calcium levels and preserves endothelial migration in the presence of lysoPC.
publishDate 2017
dc.date.none.fl_str_mv 2017-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/48812
Chaudhuri, Pinaki; Rosenbaum, Michael A.; Birnbaumer, Lutz; Graham, Linda M.; Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization; American Physiological Society; American Journal of Physiology-cell Physiology; 313; 5; 11-2017; 541-555
0363-6143
CONICET Digital
CONICET
url http://hdl.handle.net/11336/48812
identifier_str_mv Chaudhuri, Pinaki; Rosenbaum, Michael A.; Birnbaumer, Lutz; Graham, Linda M.; Integration of TRPC6 and NADPH oxidase activation in lysophosphatidylcholine-induced TRPC5 externalization; American Physiological Society; American Journal of Physiology-cell Physiology; 313; 5; 11-2017; 541-555
0363-6143
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.physiology.org/doi/10.1152/ajpcell.00028.2017
info:eu-repo/semantics/altIdentifier/doi/10.1152/ajpcell.00028.2017
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842268891275853824
score 13.13397

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