Selective inhibition of the uptake by bloodstream form Trypanosoma brucei brucei of serum lipoprotein-associated phospholipid and cholesteryl ester.
To further define how culture-adapted bloodstream form Trypanosoma brucei brucei take up lipoprotein-associated 3H-labelled lipids, external effectors were included in the incubation mixtures and assessed for their ability to influence lipid uptake. Serum molecules of 30-85 kDa, which could be replaced by albumin, selectively inhibited the uptake by culture-adapted T. b. brucei of lipoprotein-associated phospholipid and enhanced the uptake of lipoprotein-associated cholesteryl ester and cholesteryl ether. In contrast, both bile acids and protein synthesis inhibitors exerted a greater inhibitory effect on the uptake by T. b. brucei of lipoprotein-associated cholesteryl ester and cholesteryl ether than on the uptake of lipoprotein-associated phospholipid. Investigations into the mode of action of the inhibitors suggested that T. b. brucei induces release of lipoprotein-associated phospholipid prior to its uptake and that albumin binds free phospholipid, thus reducing its uptake by the T. b. brucei. The bile acids reduced parasite cholesteryl ester uptake by acting directly on the trypanosomes and did not either influence parasite protein synthesis or disrupt lipoprotein particles at the concentrations used.
Vandeweerd
V
V
International Laboratory for Research on Animal Diseases, Nairobi, Kenya.
Black
S J
SJ
D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008095:Lithocholic Acid / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D010740:Phospholipases / Q000037:antagonists & inhibitors; D010743:Phospholipids / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000378:metabolism*
D001647:Bile Acids and Salts; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D010743:Phospholipids; D011480:Protease Inhibitors; D008095:Lithocholic Acid; D003513:Cycloheximide; D010740:Phospholipases; D010744:Phosphoric Monoester Hydrolases