Effects of sterol biosynthesis inhibitors on endosymbiont-bearing trypanosomatids.
Some protozoa of the Trypanosomatidae family have a close relationship with an endosymbiotic bacterium. As the prokaryote envelope has a controversial origin, a sterol 24-methyltransferase inhibitor (20-piperidin-2-yl-5alpha-pregnan-3beta,20-diol; 22,26-azasterol) was used as a tool to investigate lipid biosynthetic pathways in Crithidia deanei, an endosymbiont-bearing trypanosomatid. Apart from antiproliferative effects, this drug induced ultrastructural alterations, consisting of myelin-like figures in the cytoplasm and endosymbiont envelope vesiculation. Concurrently, a dramatic reduction of 24-alkyl sterols was observed after 22,26-azasterol treatment, both in whole cell homogenates, as well as in isolated mitochondria. These effects were associated with changes of phospholipid composition, in particular a reduction of the phosphatidylcholine content and a concomitant increase in phosphatidylethanolamine levels. Lipid analyses of purified endosymbionts indicated a complete absence of sterols, and their phospholipid composition was different from that of mitochondria or whole protozoa, being similar to eubacteria closely associated with eukaryotes.
Palmié-Peixoto
Isabella Vieira
IV
Laboratório de Ultraestrutura Celular Hertha Meyer, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Rocha
Marcia Rosa
MR
Urbina
Julio A
JA
de Souza
Wanderley
W
Einicker-Lamas
Marcelo
M
Motta
Maria Cristina Machado
MC
D000818:Animals; D001419:Bacteria / Q000737:chemistry / Q000187:drug effects*; D004083:Cholestanol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D013261:Sterols / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D013559:Symbiosis; D014351:Trypanosomatina / Q000378:metabolism / Q000382:microbiology* / Q000648:ultrastructure
C103731:22,26-azasterol; D004791:Enzyme Inhibitors; D013261:Sterols; D004083:Cholestanol