Nonsteroidal anti-inflammatory drugs inhibit vascular smooth muscle cell proliferation by enabling the Ca2+-dependent inactivation of calcium release-activated calcium/Orai channels normally prevented by mitocondria

Producción Científica

Detalles Bibliográficos
Autores: Muñoz Conejero, Eva, Valero, Ruth Ana, Quintana, Ariel, Hoth, Markus, Núñez Llorente, Lucía, Villalobos Jorge, Carlos
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2011
País:España
Institución:Universidad de Valladolid
Repositorio:UVaDOC. Repositorio Documental de la Universidad de Valladolid
OAI Identifier:oai:uvadoc.uva.es:10324/45068
Acceso en línea:https://doi.org/10.1074/jbc.M110.198952
http://uvadoc.uva.es/handle/10324/45068
Access Level:acceso abierto
Palabra clave:Calcium channels
Canales de calcio
Mitochondria
Mitocondrias
Vascular smooth muscle
Músculo liso vascular
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spelling Nonsteroidal anti-inflammatory drugs inhibit vascular smooth muscle cell proliferation by enabling the Ca2+-dependent inactivation of calcium release-activated calcium/Orai channels normally prevented by mitocondriaMuñoz Conejero, EvaValero, Ruth AnaQuintana, ArielHoth, MarkusNúñez Llorente, LucíaVillalobos Jorge, CarlosCalcium channelsCanales de calcioMitochondriaMitocondriasVascular smooth muscleMúsculo liso vascularProducción CientíficaAbnormal vascular smooth muscle cell (VSMC) proliferation contributes to occlusive and proliferative disorders of the vessel wall. Salicylate and other nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit VSMC proliferation by an unknown mechanism unrelated to anti-inflammatory activity. In search for this mechanism, we have studied the effects of salicylate and other NSAIDs on subcellular Ca2+ homeostasis and Ca2+-dependent cell proliferation in rat aortic A10 cells, a model of neointimal VSMCs. We found that A10 cells displayed both store-operated Ca2+ entry (SOCE) and voltage-operated Ca2+ entry (VOCE), the former being more important quantitatively than the latter. Inhibition of SOCE by specific Ca2+ released-activated Ca2+ (CRAC/Orai) channels antagonists prevented A10 cell proliferation. Salicylate and other NSAIDs, including ibuprofen, indomethacin, and sulindac, inhibited SOCE and thereby Ca2+-dependent, A10 cell proliferation. SOCE, but not VOCE, induced mitochondrial Ca2+ uptake in A10 cells, and mitochondrial depolarization prevented SOCE, thus suggesting that mitochondrial Ca2+ uptake controls SOCE (but not VOCE) in A10 cells. NSAIDs depolarized mitochondria and prevented mitochondrial Ca2+ uptake, suggesting that they favor the Ca2+-dependent inactivation of CRAC/Orai channels. NSAIDs also inhibited SOCE in rat basophilic leukemia cells where mitochondrial control of CRAC/Orai is well established. NSAIDs accelerate slow inactivation of CRAC currents in rat basophilic leukemia cells under weak Ca2+ buffering conditions but not in strong Ca2+ buffer, thus excluding that NSAIDs inhibit SOCE directly. Taken together, our results indicate that NSAIDs inhibit VSMC proliferation by facilitating the Ca2+-dependent inactivation of CRAC/Orai channels which normally is prevented by mitochondria clearing of entering Ca2+.Junta de Castilla y León (grants SAN191/VA1806 and CSI12A08)Ministerio de Ciencia, Innovación y Universidades (grant BFU2009-0867)Deutsche Forschungsgemeinschaft (grant A3)Elsevier2011info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://doi.org/10.1074/jbc.M110.198952http://uvadoc.uva.es/handle/10324/45068reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolidinstname:Universidad de ValladolidIngléshttps://www.sciencedirect.com/science/article/pii/S0021925820514361?via%3Dihubinfo:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-nd/3.0/oai:uvadoc.uva.es:10324/450682026-06-13T12:44:47Z
dc.title.none.fl_str_mv Nonsteroidal anti-inflammatory drugs inhibit vascular smooth muscle cell proliferation by enabling the Ca2+-dependent inactivation of calcium release-activated calcium/Orai channels normally prevented by mitocondria
title Nonsteroidal anti-inflammatory drugs inhibit vascular smooth muscle cell proliferation by enabling the Ca2+-dependent inactivation of calcium release-activated calcium/Orai channels normally prevented by mitocondria
spellingShingle Nonsteroidal anti-inflammatory drugs inhibit vascular smooth muscle cell proliferation by enabling the Ca2+-dependent inactivation of calcium release-activated calcium/Orai channels normally prevented by mitocondria
Muñoz Conejero, Eva
Calcium channels
Canales de calcio
Mitochondria
Mitocondrias
Vascular smooth muscle
Músculo liso vascular
title_short Nonsteroidal anti-inflammatory drugs inhibit vascular smooth muscle cell proliferation by enabling the Ca2+-dependent inactivation of calcium release-activated calcium/Orai channels normally prevented by mitocondria
title_full Nonsteroidal anti-inflammatory drugs inhibit vascular smooth muscle cell proliferation by enabling the Ca2+-dependent inactivation of calcium release-activated calcium/Orai channels normally prevented by mitocondria
title_fullStr Nonsteroidal anti-inflammatory drugs inhibit vascular smooth muscle cell proliferation by enabling the Ca2+-dependent inactivation of calcium release-activated calcium/Orai channels normally prevented by mitocondria
title_full_unstemmed Nonsteroidal anti-inflammatory drugs inhibit vascular smooth muscle cell proliferation by enabling the Ca2+-dependent inactivation of calcium release-activated calcium/Orai channels normally prevented by mitocondria
title_sort Nonsteroidal anti-inflammatory drugs inhibit vascular smooth muscle cell proliferation by enabling the Ca2+-dependent inactivation of calcium release-activated calcium/Orai channels normally prevented by mitocondria
dc.creator.none.fl_str_mv Muñoz Conejero, Eva
Valero, Ruth Ana
Quintana, Ariel
Hoth, Markus
Núñez Llorente, Lucía
Villalobos Jorge, Carlos
author Muñoz Conejero, Eva
author_facet Muñoz Conejero, Eva
Valero, Ruth Ana
Quintana, Ariel
Hoth, Markus
Núñez Llorente, Lucía
Villalobos Jorge, Carlos
author_role author
author2 Valero, Ruth Ana
Quintana, Ariel
Hoth, Markus
Núñez Llorente, Lucía
Villalobos Jorge, Carlos
author2_role author
author
author
author
author
dc.subject.none.fl_str_mv Calcium channels
Canales de calcio
Mitochondria
Mitocondrias
Vascular smooth muscle
Músculo liso vascular
topic Calcium channels
Canales de calcio
Mitochondria
Mitocondrias
Vascular smooth muscle
Músculo liso vascular
description Producción Científica
publishDate 2011
dc.date.none.fl_str_mv 2011
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://doi.org/10.1074/jbc.M110.198952
http://uvadoc.uva.es/handle/10324/45068
url https://doi.org/10.1074/jbc.M110.198952
http://uvadoc.uva.es/handle/10324/45068
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://www.sciencedirect.com/science/article/pii/S0021925820514361?via%3Dihub
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/3.0/
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/3.0/
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:UVaDOC. Repositorio Documental de la Universidad de Valladolid
instname:Universidad de Valladolid
instname_str Universidad de Valladolid
reponame_str UVaDOC. Repositorio Documental de la Universidad de Valladolid
collection UVaDOC. Repositorio Documental de la Universidad de Valladolid
repository.name.fl_str_mv
repository.mail.fl_str_mv
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