Genetic resistance to malaria, oxidative stress and hemoglobin oxidation.
I describe a model which posits the molecular basis of some malaria-resistance genes in the interaction between oxidized hemoglobin and membrane components. The model is supported by a considerable body of evidence which indicates that erythrocytes of genetically protected individuals (carriers of sickle cell trait, alpha- and beta-thalassemia, and G6PD deficiency) are susceptible to the increase of oxidation of hemoglobin following H2O2 release in the host cell by Plasmodium falciparum. I suggest that the irreversible interaction between oxidized hemoglobin and the red cell membrane could trigger mechanisms that: (i) reduce invasion of erythrocytes by the falciparum parasite; (ii) impair parasite survival and development within the cell; (iii) accelerate infected erythrocyte clearance by phagocytosis.
Destro Bisol
G
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Department of Animal and Human Biology, University of Rome La Sapienza, Italy. destrobisol@axrma.uniroma1.it
D000818:Animals; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D016778:Malaria, Falciparum / Q000276:immunology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010963:Plasmodium falciparum
D006454:Hemoglobins