Einicker-Lamas M, Malaquias A T, de Castro S L, Smith G A, Oliveira M M
Instituto de Biofísica Carlos Chagas Filho, UFRJ, Ilha do Fundão, Rio de Janeiro, Brazil.
Parasitol Res. 1999 Mar;85(3):232-8. doi: 10.1007/s004360050539.
Inositol has been cited as being essential for the growth of micro-organisms and animals. Its action rests mostly in the formation of a set of inositol-containing lipids, including phosphatidylinositol and its phosphorylated derivatives. To evaluate the functional responses coupled to the phosphoinositide metabolism in Trypanosoma cruzi we used myo-inositol and its six fluorinated analogues. Their uptake into epimastigotes was characterised using tritium-labeled myo-inositol and monodeoxyfluoro-myo-inositols. The analogues were tested for their ability to inhibit [3H]-myo-inositol incorporation into phosphoinositides and the proliferation of epimastigotes and amastigotes. The results showed differences between T. cruzi and mammalian systems in the responses to the fluorinated analogues. We found that the 3-, 5- and 6-fluoro analogues did not enter the cells but had an inhibitory effect on the incorporation of the radioactive inositol into lipids and on the amastigotes' and epimastigotes' replication. The most effective inhibitor, 1-D-6-deoxy-6-myo-inositol, had no effect on mammalian cell division.
肌醇被认为是微生物和动物生长所必需的。其作用主要在于形成一组含肌醇的脂质，包括磷脂酰肌醇及其磷酸化衍生物。为了评估克氏锥虫中与磷酸肌醇代谢相关的功能反应，我们使用了肌醇及其六种氟化类似物。利用氚标记的肌醇和单脱氧氟代肌醇对它们进入无鞭毛体的摄取情况进行了表征。测试了这些类似物抑制[3H] - 肌醇掺入磷酸肌醇以及抑制无鞭毛体和无鞭毛体增殖的能力。结果显示，克氏锥虫和哺乳动物系统对氟化类似物的反应存在差异。我们发现3 - 、5 - 和6 - 氟类似物不会进入细胞，但对放射性肌醇掺入脂质以及无鞭毛体和无鞭毛体的复制具有抑制作用。最有效的抑制剂1 - D - 6 - 脱氧 - 6 - 肌醇对哺乳动物细胞分裂没有影响。
