Heterotrimeric G‐protein subunit Gαi2 contributes to agonist‐sensitive apoptosis and degranulation in murine platelets. Issue 17 (5th September 2018)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: Physiological reports. Volume 6:Issue 17(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2018-09-05
• Subjects: Apoptosis -- degranulation -- G‐protein -- Gαi2 -- platelets; Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.13841
• Languages: English
• ISSNs: 2051-817X

Abstract

Abstract: G α i2, a heterotrimeric G‐protein subunit, regulates various cell functions including ion channel activity, cell differentiation, proliferation and apoptosis. Platelet‐expressed G α i2 is decisive for the extent of tissue injury following ischemia/reperfusion. However, it is not known whether G α i2 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 α II b β 3‐integrin and caspases. Using FACS analysis, we examined the impact of agonist treatment on activation and apoptosis in platelets drawn from mice lacking G α i2 and their wild‐type (WT) littermates. As a result, treatment with either thrombin (0.01 U/mL) or CoRP (2 μ g/mL or 5 μ g/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 α II b β 3‐integrin activation. These molecular alterations were significantly less pronounced in G α i2 ‐deficient platelets as compared to WT platelets. In conclusion, our data highlight a previously unreported role of G α i2 signaling in governing platelet activation and apoptosis. Abstract : Our current observations shed light on a previously unreported function of platelet Gαi2 protein, that is, the regulation of platelet survival, mediated, at least partially by agonist‐sensitive ceramide formation. Our data on Gαi2 ‐mediated platelet survival may further our understanding into the thrombo‐inflammatory role of this protein.