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: Rosi Bissinger, Elisabeth Lang, Mehrdad Ghashghaeinia, Yogesh Singh, Christine Zelenak, Birgit Fehrenbacher, Sabina Honisch, Hong Chen, Hajar Fakhri, Anja T Umbach, Guilai Liu, Rexhep Rexhepaj, Guoxing Liu, Martin Schaller, Andreas F Mack, Adrian Lupescu, Lutz Birnbaumer, Florian Lang, Syed M Qadri
• Journal: Scientific reports (Sci Rep) Vol. 6 Pg. 30925 (08 08 2016) ISSN: 2045-2322 [Electronic] England
• PMID: 27499046 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)

Chemical References

• Phosphatidylserines
• GTP-Binding Protein alpha Subunit, Gi2

Topics

• Animals
• Cell Survival
• Eryptosis
• Erythrocyte Indices
• Erythrocytes (chemistry, cytology, physiology)
• GTP-Binding Protein alpha Subunit, Gi2 (deficiency, metabolism)
• Humans
• Mice
• Mice, Knockout
• Phosphatidylserines (analysis)