Pantaleo, Antonella and Ferru, Emanuela and Carta, Franco and Valente, Elena and Pippia, Proto Gavino and Turrini, Francesco Michelangelo (2012) Effect of heterozygous beta thalassemia on the phosphorylative response to Plasmodium falciparum infection. Journal of Proteomics, Vol. 76 , p. 251-258. eISSN 1876-7737. Article.
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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.
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