AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress

Autores
Morell, Malena; Burgos, Juan Ignacio; Gonano, Luis Alberto; Vila Petroff, Martin Gerarde
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In different pathological situations, cardiac cells undergo hyperosmotic stress (HS) and cell shrinkage. This change in cellular volume has been associated with contractile dysfunction and cell death. Given that nitric oxide (NO) is a well-recognized modulator of cardiac contractility and cell survival, we evaluated whether HS increases NO production and its impact on the negative inotropic effect observed during this type of stress. Superfusing cardiac myocytes with a hypertonic solution (HS: 440 mOsm) decreased cell volume and increased NO-sensitive DAF-FM fluorescence compared with myocytes superfused with an isotonic solution (IS: 309 mOsm). When cells were exposed to HS in addition to different inhibitors: L-NAME (NO synthase inhibitor), nitroguanidine (nNOS inhibitor), and Wortmannin (eNOS inhibitor) cell shrinkage occurred in the absence of NO release, suggesting that HS activates nNOS and eNOS. Consistently, western blot analysis demonstrated that maintaining cardiac myocytes in HS promotes phosphorylation and thus, activation of nNOS and eNOS compared to myocytes maintained in IS. HS-induced nNOS and eNOS activation and NO production were also prevented by AMPK inhibition with Dorsomorphin (DORSO). In addition, the HS-induced negative inotropic effect was exacerbated in the presence of either L-NAME, DORSO, ODQ (guanylate cyclase inhibitor), or KT5823 (PKG inhibitor), suggesting that NO provides contractile support via a cGMP/PKG-dependent mechanism. Our findings suggest a novel mechanism of AMPK-dependent NO release in cardiac myocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hyperosmotic stress.
Fil: Morell, Malena. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Burgos, Juan Ignacio. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Gonano, Luis Alberto. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Vila Petroff, Martin Gerarde. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Materia
AMPK
CONTRACTILE DYSFUNCTION
HYPEROSMOTIC STRESS
NITRIC OXIDE
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:11336/96376

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network_name_str CONICET Digital (CONICET)
spelling AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stressMorell, MalenaBurgos, Juan IgnacioGonano, Luis AlbertoVila Petroff, Martin GerardeAMPKCONTRACTILE DYSFUNCTIONHYPEROSMOTIC STRESSNITRIC OXIDEhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3In different pathological situations, cardiac cells undergo hyperosmotic stress (HS) and cell shrinkage. This change in cellular volume has been associated with contractile dysfunction and cell death. Given that nitric oxide (NO) is a well-recognized modulator of cardiac contractility and cell survival, we evaluated whether HS increases NO production and its impact on the negative inotropic effect observed during this type of stress. Superfusing cardiac myocytes with a hypertonic solution (HS: 440 mOsm) decreased cell volume and increased NO-sensitive DAF-FM fluorescence compared with myocytes superfused with an isotonic solution (IS: 309 mOsm). When cells were exposed to HS in addition to different inhibitors: L-NAME (NO synthase inhibitor), nitroguanidine (nNOS inhibitor), and Wortmannin (eNOS inhibitor) cell shrinkage occurred in the absence of NO release, suggesting that HS activates nNOS and eNOS. Consistently, western blot analysis demonstrated that maintaining cardiac myocytes in HS promotes phosphorylation and thus, activation of nNOS and eNOS compared to myocytes maintained in IS. HS-induced nNOS and eNOS activation and NO production were also prevented by AMPK inhibition with Dorsomorphin (DORSO). In addition, the HS-induced negative inotropic effect was exacerbated in the presence of either L-NAME, DORSO, ODQ (guanylate cyclase inhibitor), or KT5823 (PKG inhibitor), suggesting that NO provides contractile support via a cGMP/PKG-dependent mechanism. Our findings suggest a novel mechanism of AMPK-dependent NO release in cardiac myocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hyperosmotic stress.Fil: Morell, Malena. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Burgos, Juan Ignacio. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Gonano, Luis Alberto. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaFil: Vila Petroff, Martin Gerarde. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; ArgentinaDr Dietrich Steinkopff Verlag2018-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/96376Morell, Malena; Burgos, Juan Ignacio; Gonano, Luis Alberto; Vila Petroff, Martin Gerarde; AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress; Dr Dietrich Steinkopff Verlag; Basic Research In Cardiology; 113; 7; 1-2018; 1-110300-8428CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://link.springer.com/10.1007/s00395-017-0665-7info:eu-repo/semantics/altIdentifier/doi/10.1007/s00395-017-0665-7info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:47:54Zoai:ri.conicet.gov.ar:11336/96376instacron: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:34982025-09-29 10:47:54.748CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
title AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
spellingShingle AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
Morell, Malena
AMPK
CONTRACTILE DYSFUNCTION
HYPEROSMOTIC STRESS
NITRIC OXIDE
title_short AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
title_full AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
title_fullStr AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
title_full_unstemmed AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
title_sort AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress
dc.creator.none.fl_str_mv Morell, Malena
Burgos, Juan Ignacio
Gonano, Luis Alberto
Vila Petroff, Martin Gerarde
author Morell, Malena
author_facet Morell, Malena
Burgos, Juan Ignacio
Gonano, Luis Alberto
Vila Petroff, Martin Gerarde
author_role author
author2 Burgos, Juan Ignacio
Gonano, Luis Alberto
Vila Petroff, Martin Gerarde
author2_role author
author
author
dc.subject.none.fl_str_mv AMPK
CONTRACTILE DYSFUNCTION
HYPEROSMOTIC STRESS
NITRIC OXIDE
topic AMPK
CONTRACTILE DYSFUNCTION
HYPEROSMOTIC STRESS
NITRIC OXIDE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv In different pathological situations, cardiac cells undergo hyperosmotic stress (HS) and cell shrinkage. This change in cellular volume has been associated with contractile dysfunction and cell death. Given that nitric oxide (NO) is a well-recognized modulator of cardiac contractility and cell survival, we evaluated whether HS increases NO production and its impact on the negative inotropic effect observed during this type of stress. Superfusing cardiac myocytes with a hypertonic solution (HS: 440 mOsm) decreased cell volume and increased NO-sensitive DAF-FM fluorescence compared with myocytes superfused with an isotonic solution (IS: 309 mOsm). When cells were exposed to HS in addition to different inhibitors: L-NAME (NO synthase inhibitor), nitroguanidine (nNOS inhibitor), and Wortmannin (eNOS inhibitor) cell shrinkage occurred in the absence of NO release, suggesting that HS activates nNOS and eNOS. Consistently, western blot analysis demonstrated that maintaining cardiac myocytes in HS promotes phosphorylation and thus, activation of nNOS and eNOS compared to myocytes maintained in IS. HS-induced nNOS and eNOS activation and NO production were also prevented by AMPK inhibition with Dorsomorphin (DORSO). In addition, the HS-induced negative inotropic effect was exacerbated in the presence of either L-NAME, DORSO, ODQ (guanylate cyclase inhibitor), or KT5823 (PKG inhibitor), suggesting that NO provides contractile support via a cGMP/PKG-dependent mechanism. Our findings suggest a novel mechanism of AMPK-dependent NO release in cardiac myocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hyperosmotic stress.
Fil: Morell, Malena. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Burgos, Juan Ignacio. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Gonano, Luis Alberto. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
Fil: Vila Petroff, Martin Gerarde. Universidad Nacional de La Plata. Facultad de Ciencias Médicas; Argentina
description In different pathological situations, cardiac cells undergo hyperosmotic stress (HS) and cell shrinkage. This change in cellular volume has been associated with contractile dysfunction and cell death. Given that nitric oxide (NO) is a well-recognized modulator of cardiac contractility and cell survival, we evaluated whether HS increases NO production and its impact on the negative inotropic effect observed during this type of stress. Superfusing cardiac myocytes with a hypertonic solution (HS: 440 mOsm) decreased cell volume and increased NO-sensitive DAF-FM fluorescence compared with myocytes superfused with an isotonic solution (IS: 309 mOsm). When cells were exposed to HS in addition to different inhibitors: L-NAME (NO synthase inhibitor), nitroguanidine (nNOS inhibitor), and Wortmannin (eNOS inhibitor) cell shrinkage occurred in the absence of NO release, suggesting that HS activates nNOS and eNOS. Consistently, western blot analysis demonstrated that maintaining cardiac myocytes in HS promotes phosphorylation and thus, activation of nNOS and eNOS compared to myocytes maintained in IS. HS-induced nNOS and eNOS activation and NO production were also prevented by AMPK inhibition with Dorsomorphin (DORSO). In addition, the HS-induced negative inotropic effect was exacerbated in the presence of either L-NAME, DORSO, ODQ (guanylate cyclase inhibitor), or KT5823 (PKG inhibitor), suggesting that NO provides contractile support via a cGMP/PKG-dependent mechanism. Our findings suggest a novel mechanism of AMPK-dependent NO release in cardiac myocytes with putative pathophysiological relevance determined, at least in part, by its capability to reduce the extent of contractile dysfunction associated with hyperosmotic stress.
publishDate 2018
dc.date.none.fl_str_mv 2018-01
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/11336/96376
Morell, Malena; Burgos, Juan Ignacio; Gonano, Luis Alberto; Vila Petroff, Martin Gerarde; AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress; Dr Dietrich Steinkopff Verlag; Basic Research In Cardiology; 113; 7; 1-2018; 1-11
0300-8428
CONICET Digital
CONICET
url http://hdl.handle.net/11336/96376
identifier_str_mv Morell, Malena; Burgos, Juan Ignacio; Gonano, Luis Alberto; Vila Petroff, Martin Gerarde; AMPK-dependent nitric oxide release provides contractile support during hyperosmotic stress; Dr Dietrich Steinkopff Verlag; Basic Research In Cardiology; 113; 7; 1-2018; 1-11
0300-8428
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://link.springer.com/10.1007/s00395-017-0665-7
info:eu-repo/semantics/altIdentifier/doi/10.1007/s00395-017-0665-7
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
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Dr Dietrich Steinkopff Verlag
publisher.none.fl_str_mv Dr Dietrich Steinkopff Verlag
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
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