Reduced transglutaminase-catalyzed cross-linking of exogenous amines to membrane proteins in sickle erythrocytes.
In order to determine the capacity of sickle cells to undergo transglutaminase-catalyzed cross-linking of membrane proteins, human normal and sickle erythrocytes were incubated with [ring-2-14C]histamine in the presence of Ca2+ and ionophore A23187. The [14C]histamine incorporation into membrane components was observed in freshly prepared erythrocytes. Incorporation of radioactivity into spectrin and Band 3 membrane components was significantly (P less than 0.001) less in sickle erythrocytes than in normal cells. Transglutaminase deficiency was excluded by the finding of increased activity of this enzyme in sickle cells from patients with reticulocytosis. The incorporation of [3H]spermine into red cell membranes was also less in sickle erythrocytes than in normal cells under the same conditions of incubation used for [ring-2-14C]histamine. Sickle erythrocytes were more permeable to these amines than normal cells. It is proposed that the gamma-glutamyl sites of membrane proteins in sickle erythrocytes are less accessible for transglutaminase-catalyzed cross-linking to histamine and polyamines in vitro, perhaps due to prior in vivo activation of this enzyme by the increased calcium in sickle cells and/or shielding secondary to altered membrane organization.
Ballas
S K
SK
Mohandas
N
N
Clark
M R
MR
Embury
S H
SH
Smith
E D
ED
Marton
L J
LJ
Shohet
S B
SB
D000217:Acyltransferases / Q000378:metabolism*; D000755:Anemia, Sickle Cell / Q000097:blood*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability; D004910:Erythrocyte Membrane / Q000378:metabolism*; D006632:Histamine / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism; D013096:Spermine / Q000378:metabolism; D011503:Transglutaminases
D008565:Membrane Proteins; D011073:Polyamines; D013096:Spermine; D000001:Calcimycin; D006632:Histamine; D000217:Acyltransferases; D011503:Transglutaminases; D002118:Calcium