title: Expression of Plasmodium falciparum G6PD-6PGL in laboratory parasites and in patient isolates in G6PD-deficient and normal Nigerian children.
abstract: As the production of NADPH in the pentose phosphate pathway is the main antioxidant defence mechanism available to the Plasmodium falciparum, we have studied the expression of P. falciparum glucose 6-phosphate dehydrogenase-6-phosphogluconolactonase (PfG6PD-6PGL) in G6PD-deficient and normal erythrocyte host cells. Both erythrocytes infected in vitro with a laboratory isolate and erythrocytes from natural human infections were used. Total RNA was prepared from parasites collected from five G6PD-deficient and nine G6PD-normal children in Ibadan, Nigeria, selected after screening 189 rural schoolchildren and 68 clinical malaria patients, and was subjected to Northern blot analysis. The probe was a cDNA fragment of the G6PD domain of the PfG6PD-6PGL gene, with an internal control probe of P. falciparum 18S ribosomal RNA. Quantification was performed using a phosphoimager. Relative to internal control, the abundance of PfG6PD-6PGL mRNA (mean +/- standard deviation) was lower in parasites from G6PD-deficient children (0.29 +/- 0.27) than in G6PD-normal control subjects (0.74 +/- 0.26) (P = 0.014, Mann-Whitney U-test). Although confirmation in a larger study is required, our results suggest a lower relative abundance of PfG6PD-6PGL, and presumably antioxidant activity, in malaria parasites from G6PD-deficient hosts, thus extending the current knowledge of the mechanism of G6PD-deficiency related host protection.
authors.affiliation: Department of Haematology, Division of Investigative Science, Faculty of Medicine, Imperial College School of Medicine, Hammersmith Hospital, London W12 0NN, UK. o.sodeinde@ic.ac.uk
authors.forename: Olugbemiro
authors.initials: O
authors.lastname: Sodeinde
authors.forename: Julia L
authors.initials: JL
authors.lastname: Clarke
authors.forename: Tom J
authors.initials: TJ
authors.lastname: Vulliamy
authors.forename: Lucio
authors.initials: L
authors.lastname: Luzzatto
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Mason
mesh_terms: D000818:Animals; D002265:Carboxylic Ester Hydrolases / Q000096:biosynthesis* / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D004912:Erythrocytes / Q000201:enzymology / Q000469:parasitology / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D005954:Glucosephosphate Dehydrogenase / Q000096:biosynthesis* / Q000235:genetics; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000150:complications / Q000201:enzymology*; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000150:complications / Q000201:enzymology*; D010963:Plasmodium falciparum / Q000201:enzymology*; D012333:RNA, Messenger / Q000235:genetics; D016053:RNA, Protozoan / Q000235:genetics; D015203:Reproducibility of Results
chemical_list: D012333:RNA, Messenger; D016053:RNA, Protozoan; D005954:Glucosephosphate Dehydrogenase; D002265:Carboxylic Ester Hydrolases; C022363:6-phosphogluconolactonase