Differential effects of chloroquine on the phospholipid metabolism of Plasmodium-infected erythrocytes.
The effect of the antimalarial drug chloroquine (CQ) on the phospholipid metabolism in Plasmodium knowlesi-infected simian erythrocytes has been studied by incubating cells with different labeled precursors and various concentrations of CQ. The drug induced considerable modifications of this metabolism but at the same time decreased nucleic acid and protein synthesis as well as the output of 14CO2 from radioactive glucose. Phosphatidylcholine biosynthesis was severely reduced. However, under these conditions, CQ had the early effect of markedly increasing phosphatidylinositol labeling from radioactive inositol, fatty acids, 1-(14C)palmitoyl-lysophosphatidylcholine, but not from glycerol. Synthesis of phosphatidylserine from (14C)serine and of phosphatidylethanolamine from labeled glycerol, ethanolamine, and serine was increased, especially at high CQ concentrations when the whole metabolism of the parasite was severely reduced. These effects reflect a deep differential effect of CQ on the intense phospholipid metabolism of the Plasmodium-infected erythrocytes, which might involve a redirecting of phospholipid metabolism similar to that induced by other cationic amphiphilic drugs, and a compensatory synthesis resulting from the severe blockage of phosphatidylcholine synthesis.
Vial
H J
HJ
CNRS UA 530, INSERM U 58, Montpellier, France.
Ancelin
M L
ML
Thuet
M J
MJ
Philippot
J R
JR
D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007532:Isoleucine / Q000378:metabolism; D008252:Macaca fascicularis; D008288:Malaria / Q000097:blood*; D010743:Phospholipids / Q000097:blood*; D010961:Plasmodium
D005227:Fatty Acids; D007042:Hypoxanthines; D010743:Phospholipids; D007532:Isoleucine; D019271:Hypoxanthine; D002738:Chloroquine