1. Effect of heterozygous beta thalassemia on the phosphorylative response to Plasmodium falciparum infection.
- Author
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Pantaleo A, Ferru E, Carta F, Valente E, Pippia P, and Turrini F
- Subjects
- Adult, Erythrocyte Membrane genetics, Erythrocyte Membrane parasitology, Female, Humans, Malaria, Falciparum genetics, Male, Oxidation-Reduction, Oxidative Stress, Phosphorylation, beta-Thalassemia genetics, beta-Thalassemia parasitology, Erythrocyte Membrane metabolism, Heterozygote, Malaria, Falciparum metabolism, Membrane Proteins metabolism, Phosphoproteins metabolism, Plasmodium falciparum metabolism, beta-Thalassemia metabolism
- Abstract
Malaria parasites interact with the host cell membrane inserting new proteins and inducing oxidative and phosphorylative changes of erythrocyte proteins. In the present report we monitored the time dependent oxidative and phosphorylative modifications induced by parasites in heterozygous beta thalassemia (Het-βThal). Het-βThal causes mild anemia and is known to determine a pro-oxidant milieu and a protective effect against severe malaria. In malaria cultures Het-βThal has been reported to induce accumulation of hemoglobin denaturation products. At early parasite development stages (rings), tyrosine hyper-phosphorylation of band 3 was the most notable modification, and at later development stages (trophozoites), additional membrane proteins displayed significant hyper-phosphorylation of their serine and tyrosine residues (adducins, ankyrin, catalase). Het-βThal also caused membrane destabilization. Free radical scavengers effectively inhibited the phosphorylative response and membrane destabilization. Kinase inhibitors exerted similar effects suggesting a causal relationship between oxidative stress, membrane protein hyper-phosphorylation and increased membrane damage exacerbated by Het-βThal. In conclusion, different lines of evidence suggest that Het-βThal enhances the redox stress caused by malaria parasites inducing its protective effect destabilizing the host cell membrane. This article is part of a Special Issue entitled: Integrated omics., (Copyright © 2012 Elsevier B.V. All rights reserved.)
- Published
- 2012
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