Chloroquine-induced masking of a lipid that promotes ferriprotoporphyrin IX dimerization in malaria.
Mice infected with the NYU-2 strain of Plasmodium berghei were used to study the effect of chloroquine on masking of a lipid that promotes ferriprotoporphyrin IX dimerization. More than 40% of this lipid was masked and unable to promote dimerization in membrane ghosts from erythrocytes of untreated, infected mice. Thus, preparations of membrane ghosts dimerized 57 +/- 6 nmol of ferriprotoporphyrin IX during a 2-h incubation, whereas the lipids extracted from these preparations dimerized 101 +/- 11 nmol of ferriprotoporphyrin IX (means +/- S.D. for four experiments). Exposure of membrane ghosts to sonication or cold significantly increased the extent of masking. In addition, chloroquine treatment of infected mice increased the extent of masking to approximately 90%. The lipid could be unmasked by extracting it into acetone or by aging erythrocyte membrane ghosts from untreated or chloroquine-treated, infected mice for 24 h at pH 7.4 and 25 degrees C. These findings indicate that masking and unmasking of a lipid is central to the regulation of ferriprotoporphyrin IX dimerization in malaria parasites. They also indicate that chloroquine impairs the function of this regulatory process.
Fitch
Coy D
CD
Department of Internal Medicine, St. Louis University School of Medicine, St. Louis, Missouri 63104, USA. fitchcd@slu.edu
Chen
Yi-feng
YF
Cai
Guang-zuan
GZ
D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D002738:Chloroquine / Q000627:therapeutic use*; D019281:Dimerization; D004905:Erythrocyte Aging; D004910:Erythrocyte Membrane / Q000378:metabolism; D006427:Hemin / Q000737:chemistry* / Q000378:metabolism*; D008288:Malaria / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice
D000962:Antimalarials; D006427:Hemin; D002738:Chloroquine