Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3

Intracellular signaling pathways that are involved in protection of vascular smooth muscle cells (VSMC) from apoptosis remain poorly understood. This study examines the effect of activators of cAMP/cGMP signaling on apoptosis in non-transfected VSMC and in VSMC transfected with c-myc (VSMC-MYC) or w...

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Detalles Bibliográficos
Autores: Orlov, S.N. (Sergei N.)|||/items/49900b49-a1ad-4438-81c8-2bf8bcc6f1fa, Thorin-Trescases, N. (Nathalie)|||/items/95481e84-7d2a-46e2-9f34-38789c5b3ac8, Dulin, N.O. (Nickolai O.)|||/items/3691200f-b199-4bad-a57a-f63fc8f8291a, Dam, T.V. (Than-Vinh)|||/items/23ba2836-8e04-492b-8a17-1ee626ca7da1, Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec, Tremblay, J. (Johanne)|||/items/d29e2545-c646-4300-9687-14c59f812bbe, Hamet, P. (Pavel)|||/items/dcc7af8e-5ec3-4f2e-8627-b5bd8dba3138
Tipo de recurso: artículo
Fecha de publicación:1999
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/23232
Acceso en línea:https://hdl.handle.net/10171/23232
Access Level:acceso abierto
Palabra clave:Smooth muscle
Apoptosis
Cyclic AMP
Protein kinase A
Caspase-3
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repository_id_str
spelling Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3Orlov, S.N. (Sergei N.)|||/items/49900b49-a1ad-4438-81c8-2bf8bcc6f1faThorin-Trescases, N. (Nathalie)|||/items/95481e84-7d2a-46e2-9f34-38789c5b3ac8Dulin, N.O. (Nickolai O.)|||/items/3691200f-b199-4bad-a57a-f63fc8f8291aDam, T.V. (Than-Vinh)|||/items/23ba2836-8e04-492b-8a17-1ee626ca7da1Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ecTremblay, J. (Johanne)|||/items/d29e2545-c646-4300-9687-14c59f812bbeHamet, P. (Pavel)|||/items/dcc7af8e-5ec3-4f2e-8627-b5bd8dba3138Smooth muscleApoptosisCyclic AMPProtein kinase ACaspase-3Intracellular signaling pathways that are involved in protection of vascular smooth muscle cells (VSMC) from apoptosis remain poorly understood. This study examines the effect of activators of cAMP/cGMP signaling on apoptosis in non-transfected VSMC and in VSMC transfected with c-myc (VSMC-MYC) or with its functional analogue, E1A-adenoviral protein (VSMC-E1A). Serum-deprived VSMC-E1A exhibited the highest apoptosis measured as the content of chromatin and low molecular weight DNA fragments, phosphatidylserine content in the outer surface of plasma membrane and caspase-3 activity (ten-, five-, four- and tenfold increase after 6 h of serum withdrawal, respectively). In VSMC-E1A, the addition of an activator of adenylate cyclase, forskolin, abolished chromatin cleavage, DNA laddering, caspase-3 activation and the appearance of morphologically-defined apoptotic cells triggered by 6 h of serum deprivation. In non-transfected VSMC and in VSMC-MYC, 6 h serum deprivation led to approximately six- and threefold activation of chromatin cleavage, respectively, that was also blocked by forskolin. In VSMC-E1A, inhibition of apoptosis was observed with other activators of cAMP signaling (cholera toxin, isoproterenol, adenosine, 8-Br-cAMP), whereas 6 h incubation with modulators of cGMP signaling (8-Br-cGMP, nitroprusside, atrial natriuretic peptide, L-NAME) did not affect the development of apoptotic machinery. The antiapoptotic effect of forskolin was abolished in 24 h of serum deprivation that was accompanied by normalization of intracellular cAMP content and protein kinase A (PKA) activity. Protection of VSMC-E1A from apoptosis by forskolin was blunted by PKA inhibitors (H-89 and KT5720), whereas transfection of cells with PKA catalytic subunit attenuated apoptosis triggered by serum withdrawal. The protection of VSMC-E1A by forskolin from apoptosis was insensitive to modulators of cytoskeleton assembly (cytochalasin B, colchicine). Neither acute (30 min) nor chronic (24 h) exposure of VSMC to forskolin modified basal and serum-induced phosphorylation of the MAP kinase ERK1/2. Thus, our results show that activation of cAMP signaling delays the development of apoptosis in serum-deprived VSMC at a site upstream of caspase-3 via activation of PKA and independently of cAMP-induced reorganization of the cytoskeleton network and the ERK1/2-terminated MAPK signaling cascade.Nature Publishing GroupDadun. Depósito Académico Digital Universidad de Navarra20122012-09-2619991999-01-0119991999-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/23232reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/232322026-06-21T12:47:57Z
dc.title.none.fl_str_mv Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3
title Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3
spellingShingle Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3
Orlov, S.N. (Sergei N.)|||/items/49900b49-a1ad-4438-81c8-2bf8bcc6f1fa
Smooth muscle
Apoptosis
Cyclic AMP
Protein kinase A
Caspase-3
title_short Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3
title_full Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3
title_fullStr Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3
title_full_unstemmed Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3
title_sort Activation of cAMP signaling transiently inhibits apoptosis in vascular smooth muscle cells in a site upstream of caspase-3
dc.creator.none.fl_str_mv Orlov, S.N. (Sergei N.)|||/items/49900b49-a1ad-4438-81c8-2bf8bcc6f1fa
Thorin-Trescases, N. (Nathalie)|||/items/95481e84-7d2a-46e2-9f34-38789c5b3ac8
Dulin, N.O. (Nickolai O.)|||/items/3691200f-b199-4bad-a57a-f63fc8f8291a
Dam, T.V. (Than-Vinh)|||/items/23ba2836-8e04-492b-8a17-1ee626ca7da1
Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
Tremblay, J. (Johanne)|||/items/d29e2545-c646-4300-9687-14c59f812bbe
Hamet, P. (Pavel)|||/items/dcc7af8e-5ec3-4f2e-8627-b5bd8dba3138
author Orlov, S.N. (Sergei N.)|||/items/49900b49-a1ad-4438-81c8-2bf8bcc6f1fa
author_facet Orlov, S.N. (Sergei N.)|||/items/49900b49-a1ad-4438-81c8-2bf8bcc6f1fa
Thorin-Trescases, N. (Nathalie)|||/items/95481e84-7d2a-46e2-9f34-38789c5b3ac8
Dulin, N.O. (Nickolai O.)|||/items/3691200f-b199-4bad-a57a-f63fc8f8291a
Dam, T.V. (Than-Vinh)|||/items/23ba2836-8e04-492b-8a17-1ee626ca7da1
Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
Tremblay, J. (Johanne)|||/items/d29e2545-c646-4300-9687-14c59f812bbe
Hamet, P. (Pavel)|||/items/dcc7af8e-5ec3-4f2e-8627-b5bd8dba3138
author_role author
author2 Thorin-Trescases, N. (Nathalie)|||/items/95481e84-7d2a-46e2-9f34-38789c5b3ac8
Dulin, N.O. (Nickolai O.)|||/items/3691200f-b199-4bad-a57a-f63fc8f8291a
Dam, T.V. (Than-Vinh)|||/items/23ba2836-8e04-492b-8a17-1ee626ca7da1
Fortuño-Cebamanos, M.A. (María Antonia)|||/items/4dc78327-206a-4160-a352-90965670b0ec
Tremblay, J. (Johanne)|||/items/d29e2545-c646-4300-9687-14c59f812bbe
Hamet, P. (Pavel)|||/items/dcc7af8e-5ec3-4f2e-8627-b5bd8dba3138
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Smooth muscle
Apoptosis
Cyclic AMP
Protein kinase A
Caspase-3
topic Smooth muscle
Apoptosis
Cyclic AMP
Protein kinase A
Caspase-3
description Intracellular signaling pathways that are involved in protection of vascular smooth muscle cells (VSMC) from apoptosis remain poorly understood. This study examines the effect of activators of cAMP/cGMP signaling on apoptosis in non-transfected VSMC and in VSMC transfected with c-myc (VSMC-MYC) or with its functional analogue, E1A-adenoviral protein (VSMC-E1A). Serum-deprived VSMC-E1A exhibited the highest apoptosis measured as the content of chromatin and low molecular weight DNA fragments, phosphatidylserine content in the outer surface of plasma membrane and caspase-3 activity (ten-, five-, four- and tenfold increase after 6 h of serum withdrawal, respectively). In VSMC-E1A, the addition of an activator of adenylate cyclase, forskolin, abolished chromatin cleavage, DNA laddering, caspase-3 activation and the appearance of morphologically-defined apoptotic cells triggered by 6 h of serum deprivation. In non-transfected VSMC and in VSMC-MYC, 6 h serum deprivation led to approximately six- and threefold activation of chromatin cleavage, respectively, that was also blocked by forskolin. In VSMC-E1A, inhibition of apoptosis was observed with other activators of cAMP signaling (cholera toxin, isoproterenol, adenosine, 8-Br-cAMP), whereas 6 h incubation with modulators of cGMP signaling (8-Br-cGMP, nitroprusside, atrial natriuretic peptide, L-NAME) did not affect the development of apoptotic machinery. The antiapoptotic effect of forskolin was abolished in 24 h of serum deprivation that was accompanied by normalization of intracellular cAMP content and protein kinase A (PKA) activity. Protection of VSMC-E1A from apoptosis by forskolin was blunted by PKA inhibitors (H-89 and KT5720), whereas transfection of cells with PKA catalytic subunit attenuated apoptosis triggered by serum withdrawal. The protection of VSMC-E1A by forskolin from apoptosis was insensitive to modulators of cytoskeleton assembly (cytochalasin B, colchicine). Neither acute (30 min) nor chronic (24 h) exposure of VSMC to forskolin modified basal and serum-induced phosphorylation of the MAP kinase ERK1/2. Thus, our results show that activation of cAMP signaling delays the development of apoptosis in serum-deprived VSMC at a site upstream of caspase-3 via activation of PKA and independently of cAMP-induced reorganization of the cytoskeleton network and the ERK1/2-terminated MAPK signaling cascade.
publishDate 1999
dc.date.none.fl_str_mv 1999
1999-01-01
1999
1999-01-01
2012
2012-09-26
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/23232
url https://hdl.handle.net/10171/23232
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 Nature Publishing Group
publisher.none.fl_str_mv Nature Publishing Group
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.301603

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