Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle

Autores
Pronsato, Lucía; Boland, Ricardo Leopoldo; Milanesi, Lorena Magdalena
Año de publicación
2011
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Apoptosis is a systematic set of events that results in cellular self-destruction without inflammation or damage to the surrounding tissue. Experimental animal data indicate that apoptosis is activated in the aged skeletal muscle, contributing to the pathogenesis of sarcopenia. Given the role played by mitochondria in the induction and regulation of programmed cell death, intensive investigations have focused on mitochondria-driven myonuclear apoptosis. We have previously demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12 muscle cells. Typical changes of apoptosis such as nuclear fragmentation, cytoskeleton disorganization, mitochondrial reorganization/dysfunction and cytochrome c release induced by H2O2, are abolished when cells are previously exposed to the hormone. In the present work, we identified molecular events that occur during the anti-apoptotic effect of testosterone on C2C12 cells. At short times of exposure to H2O2, cells exhibit a defense response showing ERK2, Akt and Bad phosphorylation and an increase of HSP70 levels. At longer treatment times with the apoptotic agent, dephosphorylation of the proteins mentioned before, cytochrome c release, PARP cleavage and DNA fragmentation occur, but when cells are treated with testosterone prior to H2O2, Bad inactivation (phosphorylation), an increase in actin levels, translocation of HSP90 to mitochondria and a decrease in Bax levels are observed, revealing that, the steroid hormone regulates the apoptotic intrinsic pathway. Although further studies are required to establish the molecular basis of sarcopenia associated to states of testosterone deficit, the data presented allow us to begin to elucidate the mechanism by which the hormone prevents apoptosis in skeletal muscle.
Fil: Pronsato, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Boland, Ricardo Leopoldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Milanesi, Lorena Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Materia
Testosterone
Apoptosis
Skeletal Muscle
Mitochondria
Intrinsic Pathway
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:11336/67910
Acceder
id CONICETDig_fd4e650890be503f606006ccb5f90d70
oai_identifier_str oai:ri.conicet.gov.ar:11336/67910
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Role of testosterone in the intrinsic apoptotic pathway of skeletal musclePronsato, LucíaBoland, Ricardo LeopoldoMilanesi, Lorena MagdalenaTestosteroneApoptosisSkeletal MuscleMitochondriaIntrinsic Pathwayhttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Apoptosis is a systematic set of events that results in cellular self-destruction without inflammation or damage to the surrounding tissue. Experimental animal data indicate that apoptosis is activated in the aged skeletal muscle, contributing to the pathogenesis of sarcopenia. Given the role played by mitochondria in the induction and regulation of programmed cell death, intensive investigations have focused on mitochondria-driven myonuclear apoptosis. We have previously demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12 muscle cells. Typical changes of apoptosis such as nuclear fragmentation, cytoskeleton disorganization, mitochondrial reorganization/dysfunction and cytochrome c release induced by H2O2, are abolished when cells are previously exposed to the hormone. In the present work, we identified molecular events that occur during the anti-apoptotic effect of testosterone on C2C12 cells. At short times of exposure to H2O2, cells exhibit a defense response showing ERK2, Akt and Bad phosphorylation and an increase of HSP70 levels. At longer treatment times with the apoptotic agent, dephosphorylation of the proteins mentioned before, cytochrome c release, PARP cleavage and DNA fragmentation occur, but when cells are treated with testosterone prior to H2O2, Bad inactivation (phosphorylation), an increase in actin levels, translocation of HSP90 to mitochondria and a decrease in Bax levels are observed, revealing that, the steroid hormone regulates the apoptotic intrinsic pathway. Although further studies are required to establish the molecular basis of sarcopenia associated to states of testosterone deficit, the data presented allow us to begin to elucidate the mechanism by which the hormone prevents apoptosis in skeletal muscle.Fil: Pronsato, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Boland, Ricardo Leopoldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Milanesi, Lorena Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaElsevier Science Inc2011-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/67910Pronsato, Lucía; Boland, Ricardo Leopoldo; Milanesi, Lorena Magdalena; Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle; Elsevier Science Inc; Bone; 48; 6; 6-2011; 288-2888756-3282CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S8756328211008489info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bone.2011.03.740info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:12Zoai:ri.conicet.gov.ar:11336/67910instacron: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 09:51:12.668CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle
title Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle
spellingShingle Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle
Pronsato, Lucía
Testosterone
Apoptosis
Skeletal Muscle
Mitochondria
Intrinsic Pathway
title_short Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle
title_full Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle
title_fullStr Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle
title_full_unstemmed Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle
title_sort Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle
dc.creator.none.fl_str_mv Pronsato, Lucía
Boland, Ricardo Leopoldo
Milanesi, Lorena Magdalena
author Pronsato, Lucía
author_facet Pronsato, Lucía
Boland, Ricardo Leopoldo
Milanesi, Lorena Magdalena
author_role author
author2 Boland, Ricardo Leopoldo
Milanesi, Lorena Magdalena
author2_role author
author
dc.subject.none.fl_str_mv Testosterone
Apoptosis
Skeletal Muscle
Mitochondria
Intrinsic Pathway
topic Testosterone
Apoptosis
Skeletal Muscle
Mitochondria
Intrinsic Pathway
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Apoptosis is a systematic set of events that results in cellular self-destruction without inflammation or damage to the surrounding tissue. Experimental animal data indicate that apoptosis is activated in the aged skeletal muscle, contributing to the pathogenesis of sarcopenia. Given the role played by mitochondria in the induction and regulation of programmed cell death, intensive investigations have focused on mitochondria-driven myonuclear apoptosis. We have previously demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12 muscle cells. Typical changes of apoptosis such as nuclear fragmentation, cytoskeleton disorganization, mitochondrial reorganization/dysfunction and cytochrome c release induced by H2O2, are abolished when cells are previously exposed to the hormone. In the present work, we identified molecular events that occur during the anti-apoptotic effect of testosterone on C2C12 cells. At short times of exposure to H2O2, cells exhibit a defense response showing ERK2, Akt and Bad phosphorylation and an increase of HSP70 levels. At longer treatment times with the apoptotic agent, dephosphorylation of the proteins mentioned before, cytochrome c release, PARP cleavage and DNA fragmentation occur, but when cells are treated with testosterone prior to H2O2, Bad inactivation (phosphorylation), an increase in actin levels, translocation of HSP90 to mitochondria and a decrease in Bax levels are observed, revealing that, the steroid hormone regulates the apoptotic intrinsic pathway. Although further studies are required to establish the molecular basis of sarcopenia associated to states of testosterone deficit, the data presented allow us to begin to elucidate the mechanism by which the hormone prevents apoptosis in skeletal muscle.
Fil: Pronsato, Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Boland, Ricardo Leopoldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
Fil: Milanesi, Lorena Magdalena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentina
description Apoptosis is a systematic set of events that results in cellular self-destruction without inflammation or damage to the surrounding tissue. Experimental animal data indicate that apoptosis is activated in the aged skeletal muscle, contributing to the pathogenesis of sarcopenia. Given the role played by mitochondria in the induction and regulation of programmed cell death, intensive investigations have focused on mitochondria-driven myonuclear apoptosis. We have previously demonstrated that testosterone protects against H2O2-induced apoptosis in C2C12 muscle cells. Typical changes of apoptosis such as nuclear fragmentation, cytoskeleton disorganization, mitochondrial reorganization/dysfunction and cytochrome c release induced by H2O2, are abolished when cells are previously exposed to the hormone. In the present work, we identified molecular events that occur during the anti-apoptotic effect of testosterone on C2C12 cells. At short times of exposure to H2O2, cells exhibit a defense response showing ERK2, Akt and Bad phosphorylation and an increase of HSP70 levels. At longer treatment times with the apoptotic agent, dephosphorylation of the proteins mentioned before, cytochrome c release, PARP cleavage and DNA fragmentation occur, but when cells are treated with testosterone prior to H2O2, Bad inactivation (phosphorylation), an increase in actin levels, translocation of HSP90 to mitochondria and a decrease in Bax levels are observed, revealing that, the steroid hormone regulates the apoptotic intrinsic pathway. Although further studies are required to establish the molecular basis of sarcopenia associated to states of testosterone deficit, the data presented allow us to begin to elucidate the mechanism by which the hormone prevents apoptosis in skeletal muscle.
publishDate 2011
dc.date.none.fl_str_mv 2011-06
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/11336/67910
Pronsato, Lucía; Boland, Ricardo Leopoldo; Milanesi, Lorena Magdalena; Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle; Elsevier Science Inc; Bone; 48; 6; 6-2011; 288-288
8756-3282
CONICET Digital
CONICET
url http://hdl.handle.net/11336/67910
identifier_str_mv Pronsato, Lucía; Boland, Ricardo Leopoldo; Milanesi, Lorena Magdalena; Role of testosterone in the intrinsic apoptotic pathway of skeletal muscle; Elsevier Science Inc; Bone; 48; 6; 6-2011; 288-288
8756-3282
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.sciencedirect.com/science/article/pii/S8756328211008489
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.bone.2011.03.740
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 Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
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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score 13.13397

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