Impaired antioxidant defense in hemoglobin E-containing erythrocytes: a mechanism protective against malaria?
Red blood cell (RBC) antioxidant defense was investigated in eight individuals with hemoglobin E (Six EE and two E-B(+) thalassemia) and compared to that in six individuals with thalassemia and ten normal subjects. Individuals with hemoglobin E had increased incubated Heinz body formation (68% +/- 18%; p less than 0.001) compared to normal and thalassemic RBC (10% +/- 2% and 11% +/- 5%, respectively). Stimulated pentose phosphate shunt activity was increased in the thalassemic and decreased in the hemoglobin E RBC as compared to normal. The 2,3-diphosphoglycerate (DPG) content of the EE RBC was increased to 5.59 +/- 0.69 mumol/ml RBC as compared to normal (4.51 +/- 0.77; p less than 0.001). In the EE RBC, there was a direct correlation between Heinz body formation and DPG content (r = 0.73). Ascorbic and dehydroascorbic acid (0.1 and 1.0 mM) were able to decrease the degree of Heinz body formation in the hemoglobin E RBC. Ascorbic acid (0.1 mM) prolonged the response of the pentose shunt. Thus impaired antioxidant defense may account for the persistence of the hemoglobin E gene in areas where malaria is endemic. Oxidant medications should be used with caution in individuals of Southeast Asian origin.
Lachant
N A
NA
Department of Medicine, Harbor-UCLA Medical Center, Torrance 90502.
Tanaka
K R
KR
D019794:2,3-Diphosphoglycerate; D000975:Antioxidants / Q000737:chemistry*; D001205:Ascorbic Acid / Q000494:pharmacology; D004163:Diphosphoglyceric Acids / Q000097:blood; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005978:Glutathione / Q000097:blood; D006366:Heinz Bodies / Q000187:drug effects / Q000648:ultrastructure; D006441:Hemoglobin A / Q000378:metabolism; D006446:Hemoglobin E / Q000378:metabolism*; D006455:Hemoglobins, Abnormal / Q000378:metabolism*; D006801:Humans; D008288:Malaria / Q000097:blood* / Q000517:prevention & control; D010427:Pentose Phosphate Pathway / Q000187:drug effects; D013789:Thalassemia / Q000097:blood*
D000975:Antioxidants; D004163:Diphosphoglyceric Acids; D006455:Hemoglobins, Abnormal; D019794:2,3-Diphosphoglycerate; D006441:Hemoglobin A; D006446:Hemoglobin E; D005978:Glutathione; D001205:Ascorbic Acid