Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G-protein subunit Gαi2

Fil: Bissinger, Rosi. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Lang, Elisabeth. University of Duesseldorf. Hepatology and Infectious Diseases. Department of Gastroenterology; Alemania Fil: Ghashghaeinia, Mehrdad. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Zelenak, Christine. Charité Medical University. Department of Internal Medicine; Alemania Fil: Fehrenbacher, Birgit. University of Tuebingen. Department of Dermatology; Alemania Fil: Honisch, Sabina. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Chen, Hong. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Fakhri, Hajar. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Umbach, Anja T. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Liu, Guilai. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Rexhepaj, Rexhep. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Rexhepaj, Rexhep. University of Bonn. Institute of Biochemistry and Molecular Biology; Alemania Fil: Liu, Guoxing. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Schaller, Martin. University of Tuebingen. Department of Dermatology; Alemania Fil: Mack, Andreas F. University of Tuebingen. Institute of Anatomy; Alemania Fil: Lupescu, Adrian. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Birnbaumer, Lutz. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Birnbaumer, Lutz. National Institute of Health. Neurobiology Laboratory; Estados Unidos Fil: Lang, Florian. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Qadri, Syed M. University of Tuebingen. Vascular Medicine and Physiology. Institute of Cardiology; Alemania Fil: Qadri, Syed M. McMaster University. Department of Pathology and Molecular Medicine; Canadá Abstract: Putative functions of the heterotrimeric G-protein subunit Gαi2-dependent signaling include ion channel regulation, cell differentiation, proliferation and apoptosis. Erythrocytes may, similar to apoptosis of nucleated cells, undergo eryptosis, characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) exposure. Eryptosis may be triggered by increased cytosolic Ca(2+) activity and ceramide. In the present study, we show that Gαi2 is expressed in both murine and human erythrocytes and further examined the survival of erythrocytes drawn from Gαi2-deficient mice (Gαi2(-/-)) and corresponding wild-type mice (Gαi2(+/+)). Our data show that plasma erythropoietin levels, erythrocyte maturation markers, erythrocyte counts, hematocrit and hemoglobin concentration were similar in Gαi2(-/-) and Gαi2(+/+) mice but the mean corpuscular volume was significantly larger in Gαi2(-/-) mice. Spontaneous PS exposure of circulating Gαi2(-/-) erythrocytes was significantly lower than that of circulating Gαi2(+/+) erythrocytes. PS exposure was significantly lower in Gαi2(-/-) than in Gαi2(+/+) erythrocytes following ex vivo exposure to hyperosmotic shock, bacterial sphingomyelinase or C6 ceramide. Erythrocyte Gαi2 deficiency further attenuated hyperosmotic shock-induced increase of cytosolic Ca(2+) activity and cell shrinkage. Moreover, Gαi2(-/-) erythrocytes were more resistant to osmosensitive hemolysis as compared to Gαi2(+/+) erythrocytes. In conclusion, Gαi2 deficiency in erythrocytes confers partial protection against suicidal cell death.