DESFERRIOXAMINE PROTECTS HUMAN RED-BLOOD-CELLS FROM HEMIN-INDUCED HEMOLYSIS

被引:27
作者
BAYSAL, E [1 ]
MONTEIRO, HP [1 ]
SULLIVAN, SG [1 ]
STERN, A [1 ]
机构
[1] NYU,SCH MED,DEPT PHARMACOL,550 1ST AVE,NEW YORK,NY 10016
关键词
Desferrioxamine; Free radicals; Hemin; Hemolysis; Red cells;
D O I
10.1016/0891-5849(90)90043-I
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hemin binding to red cell membranes, its effect on red cell hemolysis, and its interaction with desferrioxamine (DFO) in these processes were investigated. DFO interacted with hemin via the iron moiety. Blockage of the binding groups in DFO prevented interaction of DFO with hemin, implying the importance of the hydroxamic acid groups in DFO-hemin interactions. Since hemolysis is a result of hemin association with the membrane components, its binding in the presence and absence of DFO was studied. DFO strongly inhibited hemin-induced lysis in a concentration-dependent manner. With 50 μM hemin, 1 mM DFO completely inhibited lysis. Preincubation of ghost membranes with DFO (1 mM) inhibited binding of hemin (50 μM) to membranes by 42%. After ghost membranes were preincubated with hemin (50 μM), the addition of DFO (1 mM) removed 20% of the membrane-bound hemin. It is suggested that DFO may have an important role in alleviating the hemin-induced deleterious effects on the red cell membrane, especially in hemolytic anemias associated with unstable, autoxidized hemoglobins. © 1990.
引用
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页码:5 / 10
页数:6
相关论文
共 36 条
[1]  
Chou, Fitch, Mechanism of hemolysis induced by ferriprotoporphyrin IX, J. Clin. Invest., 68, pp. 672-677, (1981)
[2]  
Jacob, Brain, Dacie, Altered sulfhydryl reactivity of hemoglobins and red blood cell membranes in congenital Heinz hemolytic anemia, J. Clin. Invest., 47, pp. 2664-2677, (1968)
[3]  
Jacob, Winterhalter, Unstable hemoglobins: the role of heme loss in Heinz body formation, Proc. Nat. Acad. Sci. USA, 65, pp. 697-701, (1970)
[4]  
Jacob, Winterhalter, The role of hemoglobin heme loss in Heinz body formation: studies with partially heme-deficient hemoglobins, J. Clin. Invest., 49, pp. 2008-2016, (1970)
[5]  
Bunn, Jandl, Exchange of heme among hemoglobins and between homoglobin and albumin, J. Biol. Chem., 243, pp. 465-475, (1968)
[6]  
Kreimer-Birnbaum, Pinkerton, Bannerman, Metabolism of Haemoglobin Köln, an unstable haemoglobin, Nature, Lond., 219, pp. 494-495, (1968)
[7]  
Chou, Fitch, Hemolysis of mouse erythrocytes by ferriprotoporphyrin IX and chloroquine. Chemotherapeutic implications, J. Clin. Invest., 66, pp. 856-858, (1980)
[8]  
Brunori, Wyman, Antonini, Rossi-Fanelli, Studie on the oxidation-reduction potentials of heme proteins, J. Biol. Chem., 240, pp. 3317-3324, (1965)
[9]  
Bunn, Jandl, Exchange of heme among hemoglobin molecules, Proc. Natl. Aca. Sci. USA, 56, pp. 974-978, (1966)
[10]  
Adachi, Asakura, Interaction of serum albumin with normal and sickle hemoglobins, Biochim. Biophys. Acta, 427, pp. 536-548, (1976)