Alterations in membrane fluidity, lipid metabolism, mitochondrial activity, and lipophosphoglycan expression in pentamidine-resistant Leishmania

被引:52
作者
Robert-Gero M. [1 ]
机构
[1] Institut de Chimie des Substances Naturelles, C.N.R.S., F-91198 Gif-sur-Yvette, Avenue de la Terrasse
关键词
Lipidic Metabolism; Mitochondrial Membrane; Rhodamine; Acid Phosphatase; Polar Lipid;
D O I
10.1007/s004360050361
中图分类号
学科分类号
摘要
Cytoplasmic and mitochondrial membranes were studied in wild-type promastigotes of Leishmania donovani and L. amazonensis treated with pentamidine and in the parasites resistant to this drug. Analyses by flow cytometry showed membrane fluidification in resistant cells and a modification of the lipidic metabolism in pentamidine-treated cells and in resistant clones as compared with wild-type ones. Pentamidine decreased the amounts of membrane polar lipids, i.e., phospholipids, and neutral lipidic droplets in the cytoplasm. Perturbation of lipid constituents did not induce modifications of membrane acid phosphatase and protease activities. Lipophosphoglycan, the major cell-surface glycoconjugate, was no longer detected by Western blotting in resistant cells. The use of rhodamine 123 showed a decrease in transmembrane mitochondrial potential in wild-type cells treated with pentamidine and in resistant parasites. In conclusion, cytoplasmic and mitochondrial membranes and lipidic metabolism are altered in pentamidine-resistant parasites. © Springer-Verlag 1998.
引用
收藏
页码:78 / 83
页数:5
相关论文
共 5 条
  • [1] Basselin M., Lawrence F., Robert-Gero M., Altered transport properties of pentamidine-resistant Leishmania donovani and L. amazonensis, Parasitol Res, 83, pp. 413-418, (1997)
  • [2] Bradford M.M., A rapid and sensitive method for the quantitation of microgram quantities of proteins utilizing the principle of protein-dye binding, Anal Biochem, 116, pp. 53-64, (1976)
  • [3] Croft S.L., Urbina J.A., Brun R., Chemotherapy of human leishmaniasis and trypanosomiasis, Trypanosomiasis and Leishmaniasis, 14, pp. 245-257, (1997)
  • [4] David S.A., Bechtel B., Annaiah C., Mathan V.I., Balaram P., Interaction of cationic amphiphilic drugs with lipid A: Impli-cations for development of endotoxin antagonists, Biochim Biophys Acta, 1212, pp. 167-175, (1994)
  • [5] Fouchet P., Jayat C., Hechard Y., Ratinaud M.H., Frelat G., Recent advances of flow cytometry in fundamental and applied microbiology, Biol Cell, 78, pp. 95-109, (1993)