title: Osmotic resistance of high-density erythrocytes in transglutaminase 2-deficient mice.
abstract: Transglutaminase 2 (TGase 2) is a Ca(2+)-dependent enzyme responsible for the posttransttranslational modification of proteins by transamidation of specific polypeptide-bound glutamine residues. Elevating the intracellular concentration of Ca(2+)-ions in human erythrocytes leads to the formation of cytoskeletal and cytoplasmic protein polymers. The Ca(2+)-dependent TGase 2-dependent cross-linking activity has been proposed for its involvement in erythrocyte aging, by inducing irreversible modification of their cell shape and deformability. Accordingly, we found that high-density ("old") TGase 2(minus sign/minus sign) red blood cells (RBCs) were more resistant to osmotic stress-induced hemolysis than those from wild type mice. In addition, elevating the intracellular concentration of Ca(2+) by treatment of total RBCs with ionophore A23187 resulted in enhanced resistance of TGase 2-deficient erythrocytes compared to their normal counterpart. These findings indicate that TGase 2 may have a role in regulating structural flexibility of RBCs, possibly affecting their life span in physiopathological conditions, such as erythrocyte senescence, which are accompanied by increases in intracellular Ca(2+) concentration.
authors.affiliation: Biochemistry Laboratory, c/o Department of Experimental Medicine, University of Rome Tor Vergata, Via Tor Vergata 135, 00133 Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Bernassola
authors.forename: Giovanna
authors.initials: G
authors.lastname: Boumis
authors.forename: Marco
authors.initials: M
authors.lastname: Corazzari
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Bertini
authors.forename: Gennaro
authors.initials: G
authors.lastname: Citro
authors.forename: Richard A
authors.initials: RA
authors.lastname: Knight
authors.forename: Gino
authors.initials: G
authors.lastname: Amiconi
authors.forename: Gerry
authors.initials: G
authors.lastname: Melino
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology* / Q000502:physiology; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009997:Osmotic Pressure; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D002118:Calcium