Leishmania donovani: enhanced expression of soluble acid phosphatase in the presence of sinefungin, an antiparasitic agent.
Sinefungin, an antileishmanial nucleoside, induces morphological and ultrastructural changes in promastigotes of Leishmania donovani. The most important modifications are the enlargement of the flagellar pocket and the increased activity of the Golgi apparatus. Cytoenzymatic labeling demonstrates an increased activity of the soluble acid phosphatase in the flagellar reservoir of sinefungin-treated cells. The affinity constant remained unchanged. Analyzes by Western blot demonstrate an increased amount of the enzyme in the treated cells. The increased amount was not due to impaired enzyme release, as in the external medium the acid phosphatase was also enhanced but to a lesser extent. Under identical conditions the membrane-bound acid phosphatase was not modified. These results indicate that the enlargement of the flagellar pocket is the consequence of the accumulation of acid phosphatase and other Golgi-mediated enzyme provoking unbalanced cytoplasmic exchange. Sinefungin has the same effects on Leishmania tropica promastigotes. However, these effects are not specific to sinefungin. Another molecule, taxol, also induced cell rounding accompanied by increased acid phosphatase activity. Under conditions where cell rounding is not observed, in stationary phase or with compounds which stopped proliferation without shape change, no increase in the amount of acid phosphatase could be observed. These results clearly demonstrate a correlation between morphological, ultrastructural changes and the stimulated expression of acid phosphatase.
Moulay
L
L
Institut de Chimie des Substances Naturelles, C.N.R.S., Gif sur Yvette, France.
Robert-Gero
M
M
D000135:Acid Phosphatase / Q000096:biosynthesis* / Q000737:chemistry; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D015153:Blotting, Western; D003600:Cytosol / Q000201:enzymology; D005407:Flagella / Q000201:enzymology; D006056:Golgi Apparatus / Q000201:enzymology; D006651:Histocytochemistry; D007700:Kinetics; D007893:Leishmania donovani / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D008854:Microscopy, Electron; D008970:Molecular Weight
D000981:Antiprotozoal Agents; D000135:Acid Phosphatase; D000241:Adenosine; C006235:sinefungin