Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets

Autores
Cao, Hang; Qadri, Syed M.; Lang, Elisabeth; Pelzl, Lisann; Umbach, Anja T.; Leiss, Veronika; Birnbaumer, Lutz; Nürnberg, Bernd; Pieske, Burkert; Voelkl, Jakob; Gawaz, Meinrad; Bissinger, Rosi; Lang, Florian
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Gαi2, a heterotrimeric G-protein subunit, regulates various cell functions including ion channel activity, cell differentiation, proliferation and apoptosis. Platelet-expressed Gαi2 is decisive for the extent of tissue injury following ischemia/reperfusion. However, it is not known whether Gαi2 plays a role in the regulation of platelet apoptosis, which is characterized by caspase activation, cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) translocation to the platelet surface. Stimulators of platelet apoptosis include thrombin and collagen-related peptide (CoRP), which are further known to enhance degranulation and activation of αII bβ3-integrin and caspases. Using FACS analysis, we examined the impact of agonist treatment on activation and apoptosis in platelets drawn from mice lacking Gαi2 and their wild-type (WT) littermates. As a result, treatment with either thrombin (0.01 U/mL) or CoRP (2 μg/mL or 5 μg/mL) significantly upregulated PS-exposure and significantly decreased forward scatter, reflecting cell size, in both genotypes. Exposure to CoRP triggered a significant increase in active caspase 3, ceramide formation, surface P-selectin, and αII bβ3-integrin activation. These molecular alterations were significantly less pronounced in Gαi2-deficient platelets as compared to WT platelets. In conclusion, our data highlight a previously unreported role of Gαi2 signaling in governing platelet activation and apoptosis.
Fil: Cao, Hang. Universität Tübingen; Alemania
Fil: Qadri, Syed M.. Canadian Blood Services; Canadá. McMaster University; Canadá
Fil: Lang, Elisabeth. Heinrich-heine-universität Düsseldorf; Alemania
Fil: Pelzl, Lisann. Universität Tübingen; Alemania
Fil: Umbach, Anja T.. Universität Tübingen; Alemania
Fil: Leiss, Veronika. Universität Tübingen; Alemania
Fil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Nürnberg, Bernd. Universität Tübingen; Alemania
Fil: Pieske, Burkert. Berlin Institute of Health; Alemania. Universitätsmedizin Berlin; Alemania
Fil: Voelkl, Jakob. Berlin Institute of Health; Alemania. Universitätsmedizin Berlin; Alemania
Fil: Gawaz, Meinrad. Universität Tübingen; Alemania
Fil: Bissinger, Rosi. Universität Tübingen; Alemania
Fil: Lang, Florian. Universität Tübingen; Alemania. Heinrich-heine-universität Düsseldorf; Alemania
Materia
APOPTOSIS
DEGRANULATION
G-PROTEIN
GΑI2
PLATELETS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/99447
Acceder
id CONICETDig_d4b4b1e61a143cbd18878ebdf495bf24
oai_identifier_str oai:ri.conicet.gov.ar:11336/99447
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine plateletsCao, HangQadri, Syed M.Lang, ElisabethPelzl, LisannUmbach, Anja T.Leiss, VeronikaBirnbaumer, LutzNürnberg, BerndPieske, BurkertVoelkl, JakobGawaz, MeinradBissinger, RosiLang, FlorianAPOPTOSISDEGRANULATIONG-PROTEINGΑI2PLATELETShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Gαi2, a heterotrimeric G-protein subunit, regulates various cell functions including ion channel activity, cell differentiation, proliferation and apoptosis. Platelet-expressed Gαi2 is decisive for the extent of tissue injury following ischemia/reperfusion. However, it is not known whether Gαi2 plays a role in the regulation of platelet apoptosis, which is characterized by caspase activation, cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) translocation to the platelet surface. Stimulators of platelet apoptosis include thrombin and collagen-related peptide (CoRP), which are further known to enhance degranulation and activation of αII bβ3-integrin and caspases. Using FACS analysis, we examined the impact of agonist treatment on activation and apoptosis in platelets drawn from mice lacking Gαi2 and their wild-type (WT) littermates. As a result, treatment with either thrombin (0.01 U/mL) or CoRP (2 μg/mL or 5 μg/mL) significantly upregulated PS-exposure and significantly decreased forward scatter, reflecting cell size, in both genotypes. Exposure to CoRP triggered a significant increase in active caspase 3, ceramide formation, surface P-selectin, and αII bβ3-integrin activation. These molecular alterations were significantly less pronounced in Gαi2-deficient platelets as compared to WT platelets. In conclusion, our data highlight a previously unreported role of Gαi2 signaling in governing platelet activation and apoptosis.Fil: Cao, Hang. Universität Tübingen; AlemaniaFil: Qadri, Syed M.. Canadian Blood Services; Canadá. McMaster University; CanadáFil: Lang, Elisabeth. Heinrich-heine-universität Düsseldorf; AlemaniaFil: Pelzl, Lisann. Universität Tübingen; AlemaniaFil: Umbach, Anja T.. Universität Tübingen; AlemaniaFil: Leiss, Veronika. Universität Tübingen; AlemaniaFil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; ArgentinaFil: Nürnberg, Bernd. Universität Tübingen; AlemaniaFil: Pieske, Burkert. Berlin Institute of Health; Alemania. Universitätsmedizin Berlin; AlemaniaFil: Voelkl, Jakob. Berlin Institute of Health; Alemania. Universitätsmedizin Berlin; AlemaniaFil: Gawaz, Meinrad. Universität Tübingen; AlemaniaFil: Bissinger, Rosi. Universität Tübingen; AlemaniaFil: Lang, Florian. Universität Tübingen; Alemania. Heinrich-heine-universität Düsseldorf; AlemaniaAmerican Physiological Society2018-09info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/99447Cao, Hang; Qadri, Syed M.; Lang, Elisabeth; Pelzl, Lisann; Umbach, Anja T.; et al.; Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets; American Physiological Society; Physiological Reports; 6; 17; 9-2018; 1-82051-817XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy2.13841info:eu-repo/semantics/altIdentifier/doi/10.14814/phy2.13841info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:01:38Zoai:ri.conicet.gov.ar:11336/99447instacron: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 10:01:38.425CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets
title Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets
spellingShingle Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets
Cao, Hang
APOPTOSIS
DEGRANULATION
G-PROTEIN
GΑI2
PLATELETS
title_short Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets
title_full Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets
title_fullStr Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets
title_full_unstemmed Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets
title_sort Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets
dc.creator.none.fl_str_mv Cao, Hang
Qadri, Syed M.
Lang, Elisabeth
Pelzl, Lisann
Umbach, Anja T.
Leiss, Veronika
Birnbaumer, Lutz
Nürnberg, Bernd
Pieske, Burkert
Voelkl, Jakob
Gawaz, Meinrad
Bissinger, Rosi
Lang, Florian
author Cao, Hang
author_facet Cao, Hang
Qadri, Syed M.
Lang, Elisabeth
Pelzl, Lisann
Umbach, Anja T.
Leiss, Veronika
Birnbaumer, Lutz
Nürnberg, Bernd
Pieske, Burkert
Voelkl, Jakob
Gawaz, Meinrad
Bissinger, Rosi
Lang, Florian
author_role author
author2 Qadri, Syed M.
Lang, Elisabeth
Pelzl, Lisann
Umbach, Anja T.
Leiss, Veronika
Birnbaumer, Lutz
Nürnberg, Bernd
Pieske, Burkert
Voelkl, Jakob
Gawaz, Meinrad
Bissinger, Rosi
Lang, Florian
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv APOPTOSIS
DEGRANULATION
G-PROTEIN
GΑI2
PLATELETS
topic APOPTOSIS
DEGRANULATION
G-PROTEIN
GΑI2
PLATELETS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Gαi2, a heterotrimeric G-protein subunit, regulates various cell functions including ion channel activity, cell differentiation, proliferation and apoptosis. Platelet-expressed Gαi2 is decisive for the extent of tissue injury following ischemia/reperfusion. However, it is not known whether Gαi2 plays a role in the regulation of platelet apoptosis, which is characterized by caspase activation, cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) translocation to the platelet surface. Stimulators of platelet apoptosis include thrombin and collagen-related peptide (CoRP), which are further known to enhance degranulation and activation of αII bβ3-integrin and caspases. Using FACS analysis, we examined the impact of agonist treatment on activation and apoptosis in platelets drawn from mice lacking Gαi2 and their wild-type (WT) littermates. As a result, treatment with either thrombin (0.01 U/mL) or CoRP (2 μg/mL or 5 μg/mL) significantly upregulated PS-exposure and significantly decreased forward scatter, reflecting cell size, in both genotypes. Exposure to CoRP triggered a significant increase in active caspase 3, ceramide formation, surface P-selectin, and αII bβ3-integrin activation. These molecular alterations were significantly less pronounced in Gαi2-deficient platelets as compared to WT platelets. In conclusion, our data highlight a previously unreported role of Gαi2 signaling in governing platelet activation and apoptosis.
Fil: Cao, Hang. Universität Tübingen; Alemania
Fil: Qadri, Syed M.. Canadian Blood Services; Canadá. McMaster University; Canadá
Fil: Lang, Elisabeth. Heinrich-heine-universität Düsseldorf; Alemania
Fil: Pelzl, Lisann. Universität Tübingen; Alemania
Fil: Umbach, Anja T.. Universität Tübingen; Alemania
Fil: Leiss, Veronika. Universität Tübingen; Alemania
Fil: Birnbaumer, Lutz. National Institutes of Health; Estados Unidos. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires". Instituto de Investigaciones Biomédicas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas; Argentina
Fil: Nürnberg, Bernd. Universität Tübingen; Alemania
Fil: Pieske, Burkert. Berlin Institute of Health; Alemania. Universitätsmedizin Berlin; Alemania
Fil: Voelkl, Jakob. Berlin Institute of Health; Alemania. Universitätsmedizin Berlin; Alemania
Fil: Gawaz, Meinrad. Universität Tübingen; Alemania
Fil: Bissinger, Rosi. Universität Tübingen; Alemania
Fil: Lang, Florian. Universität Tübingen; Alemania. Heinrich-heine-universität Düsseldorf; Alemania
description Gαi2, a heterotrimeric G-protein subunit, regulates various cell functions including ion channel activity, cell differentiation, proliferation and apoptosis. Platelet-expressed Gαi2 is decisive for the extent of tissue injury following ischemia/reperfusion. However, it is not known whether Gαi2 plays a role in the regulation of platelet apoptosis, which is characterized by caspase activation, cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) translocation to the platelet surface. Stimulators of platelet apoptosis include thrombin and collagen-related peptide (CoRP), which are further known to enhance degranulation and activation of αII bβ3-integrin and caspases. Using FACS analysis, we examined the impact of agonist treatment on activation and apoptosis in platelets drawn from mice lacking Gαi2 and their wild-type (WT) littermates. As a result, treatment with either thrombin (0.01 U/mL) or CoRP (2 μg/mL or 5 μg/mL) significantly upregulated PS-exposure and significantly decreased forward scatter, reflecting cell size, in both genotypes. Exposure to CoRP triggered a significant increase in active caspase 3, ceramide formation, surface P-selectin, and αII bβ3-integrin activation. These molecular alterations were significantly less pronounced in Gαi2-deficient platelets as compared to WT platelets. In conclusion, our data highlight a previously unreported role of Gαi2 signaling in governing platelet activation and apoptosis.
publishDate 2018
dc.date.none.fl_str_mv 2018-09
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/11336/99447
Cao, Hang; Qadri, Syed M.; Lang, Elisabeth; Pelzl, Lisann; Umbach, Anja T.; et al.; Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets; American Physiological Society; Physiological Reports; 6; 17; 9-2018; 1-8
2051-817X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/99447
identifier_str_mv Cao, Hang; Qadri, Syed M.; Lang, Elisabeth; Pelzl, Lisann; Umbach, Anja T.; et al.; Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets; American Physiological Society; Physiological Reports; 6; 17; 9-2018; 1-8
2051-817X
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://physoc.onlinelibrary.wiley.com/doi/full/10.14814/phy2.13841
info:eu-repo/semantics/altIdentifier/doi/10.14814/phy2.13841
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Physiological Society
publisher.none.fl_str_mv American Physiological Society
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
_version_ 1842269708555911168
score 13.13397

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