Osmotic resistance of high-density erythrocytes in transglutaminase 2-deficient mice.
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.
Bernassola
Francesca
F
Biochemistry Laboratory, c/o Department of Experimental Medicine, University of Rome Tor Vergata, Via Tor Vergata 135, 00133 Rome, Italy.
Boumis
Giovanna
G
Corazzari
Marco
M
Bertini
Giuseppe
G
Citro
Gennaro
G
Knight
Richard A
RA
Amiconi
Gino
G
Melino
Gerry
G
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*
D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins; D002118:Calcium