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

Abstract: 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 whethe...

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Autores principales: 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
Formato: Artículo
Lenguaje:Inglés
Publicado: Wiley Open Access 2019
Materias:
APOPTOSIS
CELULAS DE LA SANGRE
REPERFUSION MIOCARDICA
Acceso en línea:https://repositorio.uca.edu.ar/handle/123456789/8687
Aporte de:
Repositorio Institucional de la Universidad Católica Argentina (UCA) de Universidad Católica Argentina
id I33-R139123456789-8687
record_format dspace
institution Universidad Católica Argentina
institution_str I-33
repository_str R-139
collection Repositorio Institucional de la Universidad Católica Argentina (UCA)
language Inglés
topic APOPTOSIS
CELULAS DE LA SANGRE
REPERFUSION MIOCARDICA
spellingShingle APOPTOSIS
CELULAS DE LA SANGRE
REPERFUSION MIOCARDICA
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
Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine platelets
topic_facet APOPTOSIS
CELULAS DE LA SANGRE
REPERFUSION MIOCARDICA
description Abstract: 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 αIIb β3-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 αIIb β3-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.
format Artículo
author 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_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_sort Cao, Hang
title Heterotrimeric G-protein subunit Gαi2 contributes to agonist-sensitive apoptosis and degranulation in murine 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
publisher Wiley Open Access
publishDate 2019
url https://repositorio.uca.edu.ar/handle/123456789/8687
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