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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/96376
Ver los metadatos del registro completo
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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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1844614524199501824 |
score |
13.070432 |