title: Effect of heterozygous beta thalassemia on the phosphorylative response to Plasmodium falciparum infection.
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.
authors.affiliation: Department of Scienze Biomediche, University of Sassari, 07100, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Pantaleo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ferru
authors.forename: Franco
authors.initials: F
authors.lastname: Carta
authors.forename: Elena
authors.initials: E
authors.lastname: Valente
authors.forename: Proto
authors.initials: P
authors.lastname: Pippia
authors.forename: Francesco
authors.initials: F
authors.lastname: Turrini
mesh_terms: D000328:Adult; D004910:Erythrocyte Membrane / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology; D005260:Female; D006579:Heterozygote; D006801:Humans; D016778:Malaria, Falciparum / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D010963:Plasmodium falciparum / Q000378:metabolism*; D017086:beta-Thalassemia / Q000235:genetics / Q000378:metabolism* / Q000469:parasitology
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins