Expression of Plasmodium falciparum G6PD-6PGL in laboratory parasites and in patient isolates in G6PD-deficient and normal Nigerian children.
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.
Sodeinde
Olugbemiro
O
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
Clarke
Julia L
JL
Vulliamy
Tom J
TJ
Luzzatto
Lucio
L
Mason
Philip J
PJ
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
D012333:RNA, Messenger; D016053:RNA, Protozoan; D005954:Glucosephosphate Dehydrogenase; D002265:Carboxylic Ester Hydrolases; C022363:6-phosphogluconolactonase