title: Blunted apoptosis of erythrocytes in mice deficient in the heterotrimeric G-protein subunit Gαi2.
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.
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Rosi
authors: R
authors: Bissinger
authors: Department of Gastroenterology, Hepatology and Infectious Diseases, University of Duesseldorf, Germany.
authors: Elisabeth
authors: E
authors: Lang
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Mehrdad
authors: M
authors: Ghashghaeinia
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Yogesh
authors: Y
authors: Singh
authors: Department of Internal Medicine, Charité Medical University, Berlin, Germany.
authors: Christine
authors: C
authors: Zelenak
authors: Department of Dermatology, University of Tuebingen, Germany.
authors: Birgit
authors: B
authors: Fehrenbacher
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Sabina
authors: S
authors: Honisch
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Hong
authors: H
authors: Chen
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Hajar
authors: H
authors: Fakhri
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Anja T
authors: AT
authors: Umbach
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Guilai
authors: G
authors: Liu
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.|Institute of Biochemistry and Molecular Biology, University of Bonn, Germany.
authors: Rexhep
authors: R
authors: Rexhepaj
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Guoxing
authors: G
authors: Liu
authors: Department of Dermatology, University of Tuebingen, Germany.
authors: Martin
authors: M
authors: Schaller
authors: Institute of Anatomy, University of Tuebingen, Germany.
authors: Andreas F
authors: AF
authors: Mack
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Adrian
authors: A
authors: Lupescu
authors: Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC, USA.
authors: Lutz
authors: L
authors: Birnbaumer
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.
authors: Florian
authors: F
authors: Lang
authors: Institute of Cardiology, Vascular Medicine and Physiology, University of Tuebingen, Germany.|Institute of Biomedical Research (BIOMED), School of Medical Sciences, Catholic University of Argentina, Buenos Aires, Argentina.|Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
authors: Syed M
authors: SM
authors: Qadri
mesh_terms: D000818:Animals; D002470:Cell Survival; D000072817:Eryptosis; D004909:Erythrocyte Indices; D004912:Erythrocytes / Q000737:chemistry / Q000166:cytology* / Q000502:physiology*; D051960:GTP-Binding Protein alpha Subunit, Gi2 / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010718:Phosphatidylserines / Q000032:analysis
chemical_list: D010718:Phosphatidylserines; D051960:GTP-Binding Protein alpha Subunit, Gi2