title: Differential carbonylation of cytoskeletal proteins in blood group O erythrocytes: potential role in protection against severe malaria.
abstract: The molecular basis for the prevalence of blood group O in regions where malaria is endemic remains unclear. In some genetic backgrounds oxidative modifications have been linked to a reduced susceptibility to severe malaria disease. Through redox proteomics, we detected differences in carbonylated membrane proteins among the different blood groups, both in Plasmodium-infected and uninfected erythrocytes (RBC). Carbonylation profiles of RBC membrane proteins revealed that group O blood shows a reduced protein oxidation pattern compared to groups A, B and AB. Upon infection with Plasmodium falciparum Dd2, erythrocytes of all blood groups showed increased oxidation of membrane proteins. By examining 4-hydroxy-2-nonenal (4-HNE) modified proteins by LC-MS/MS (liquid chromatography/mass spectrometry) we observed that, upon malaria infection, the protein components of lipid rafts and cytoskeleton were the main targets of 4-HNE carbonylation in all blood groups. Ankyrins and protein bands 4.2 and 4.1 were differentially carbonylated in group O as compared to A and B groups. During trophozoite maturation in group O erythrocytes, a steady increase was observed in the number of 4-HNE-modified proteins, suggesting a parasite-driven 4-HNE-carbonylation process. Our findings indicate a possible correlation between the protection against severe malaria in blood group O individuals and a specific pattern of 4-HNE-carbonylation of cytoskeleton proteins.
authors: Department of Biochemistry and Molecular Biology IV, Universidad Complutense de Madrid, Ciudad Universitaria, Madrid, Spain.
authors: Darío
authors: D
authors: Méndez
authors: María L
authors: ML
authors: Hernáez
authors: Ali N
authors: AN
authors: Kamali
authors: Amalia
authors: A
authors: Diez
authors: Antonio
authors: A
authors: Puyet
authors: José M
authors: JM
authors: Bautista
mesh_terms: D000017:ABO Blood-Group System / Q000502:physiology*; D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism; D016022:Case-Control Studies; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D004912:Erythrocytes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction; D010963:Plasmodium falciparum; D050050:Protein Carbonylation; D040901:Proteomics
chemical_list: D000017:ABO Blood-Group System; D000447:Aldehydes; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C027576:4-hydroxy-2-nonenal