The adaptation of Plasmodium falciparum to oxidative stress in G6PD deficient human erythrocytes.
It has recently been found that growth of P. falciparum in human G6PD deficient red cells is impaired in vitro; however, the inhibition is overcome after two or three growth cycles. There is evidence to suggest that the parasite can produce its own G6PD enzyme which may compensate for the lack of host enzyme and could account for the resumption of normal growth in G6PD deficient host cells. It is unclear whether the parasite enzyme can enable the host cell to resist oxidative stress as normal cells do. To answer this question, P. falciparum was grown in vitro in: (a) normal red cells, (b) G6PD deficient red cells for one growth cycle only, (c) G6PD deficient cells for a minimum of five cycles. All groups were then challenged with acetylphenylhydrazine (APH) which served as an oxidative stress. Both G6PD (A-) and Mediterranean deficient types were studied. The results show a two-fold increase in resistance to oxidative stress by parasites adapted to G6PD-Mediterranean deficient host cells as compared to unadapted ones, but the parasite-red cell system remains 4 times more sensitive to APH than normal infected cells. In parasitized G6PD (A-) red cells, evidence of adaptation could be seen in the growth curves, but no detectable increase in resistance to APH was found in adapted parasites. It is concluded that the role of the parasite G6PD is not likely to be mainly related to oxidative stress resistance and therefore other functions of this enzyme should be investigated.
Roth
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Division of Hematology, Montefiore Hospital and the Albert Einstein College of Medicine, Bronx, New York 10467.
Schulman
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S
D000220:Adaptation, Biological; D000818:Animals; D002478:Cells, Cultured; D004912:Erythrocytes / Q000201:enzymology / Q000469:parasitology*; D005955:Glucosephosphate Dehydrogenase Deficiency / Q000469:parasitology*; D006801:Humans; D008297:Male; D010100:Oxygen / Q000502:physiology*; D010659:Phenylhydrazines / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects / Q000254:growth & development*
D010659:Phenylhydrazines; C006384:N(1)-acetylphenylhydrazine; D010100:Oxygen