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
• Fuente: Physiological Reports. 2018;6(17):e13841
• Materia: APOPTOSIS; CELULAS DE LA SANGRE; REPERFUSION MIOCARDICA
• Institución: Pontificia Universidad Católica Argentina

Fil: Cao, Hang. Eberhard-Karls University. Department of Vegetative & Clinical Physiology; Alemania
Fil: Qadri, Syed M. McMaster University. Department of Pathology and Molecular Medicine; Canadá
Fil: Qadri, Syed M. Canadian Blood Services. Centre for Innovation
Fil: Lang, Elisabeth. Heinrich Heine University. Department of Molecular Medicine II; Alemania
Fil: Pelzl, Lisann. Eberhard-Karls University. Department of Vegetative & Clinical Physiology; Alemania
Fil: Umbach, Anja T. Eberhard-Karls University. Department of Vegetative & Clinical Physiology; Alemania
Fil: Leiss, Veronika. Eberhard-Karls University. Interfaculty Center of Pharmacology and Drug Research. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Birnbaumer, Lutz. Research Triangle Park. National Institute of Environmental Health Sciences. Neurobiology Laboratory; Estados Unidos
Fil: Birnbaumer, Lutz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina
Fil: Nürnberg, Bernd. Eberhard-Karls University. Interfaculty Center of Pharmacology and Drug Research. Department of Pharmacology and Experimental Therapy; Alemania
Fil: Pieske, Burkert. Charite-Universitätsmedizin Berlin. Department of Internal Medicine and Cardiology; Alemania
Fil: Pieske, Burkert. Berlin Institute of Health; Alemania
Fil: Pieske, Burkert. German Centre for Cardiovascular Research; Alemania
Fil: Voelkl, Jakob. Charite-Universitätsmedizin Berlin. Department of Internal Medicine and Cardiology; Alemania
Fil: Voelkl, Jakob. Berlin Institute of Health; Alemania
Fil: Voelkl, Jakob. Charite-Universitätsmedizin Berlin. Department of Internal Medicine and Cardiology; Alemania
Fil: Gawaz, Meinrad. Eberhard-Karls University. Department of Internal Medicine III; Alemania
Fil: Bissinger, Rosi. Eberhard-Karls University. Department of Internal Medicine III; Alemania
Fil: Lang, Florian. Eberhard-Karls University. Department of Vegetative & Clinical Physiology; Alemania
Fil: Lang, Florian. Heinrich Heine University. Department of Molecular Medicine II; Alemania
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.