Taylor D R, Williams G T
Department of Anatomy, University of Birmingham, Medical School, United Kingdom.
Exp Parasitol. 1988 Aug;66(2):189-96. doi: 10.1016/0014-4894(88)90090-2.
Leishmania mexicana amazonensis amastigotes were induced to differentiate by incubation at 27 C. Morphological transformation was studied both in untreated cultures and in cultures where DNA synthesis, and consequently the final stage in the production of promastigotes, was inhibited by hydroxyurea. 3-Methoxybenzamide and other antagonists of ADP-ribosyltransferase (ADPRT) specifically inhibited differentiation at a very early stage in both experimental systems. Cell proliferation (in the absence of hydroxyurea) was not inhibited by ADPRT antagonists--indeed greater multiplication of undifferentiated parasites was observed in the presence of these compounds. This indicated that the parasites were being diverted from differentiation to proliferation. Preincubation of the amastigotes with the ADPRT antagonists was required to produce this effect, providing further evidence that ADP-ribosylation of proteins is required for the initiation of differentiation in Leishmania.
将墨西哥利什曼原虫亚马逊亚种无鞭毛体在27℃孵育以诱导其分化。在未处理的培养物以及DNA合成（进而前鞭毛体产生的最后阶段）被羟基脲抑制的培养物中研究形态学转变。在两个实验系统中，3-甲氧基苯甲酰胺和其他ADP-核糖基转移酶（ADPRT）拮抗剂在非常早期阶段特异性抑制分化。ADPRT拮抗剂不抑制细胞增殖（在不存在羟基脲的情况下）——事实上，在这些化合物存在时观察到未分化寄生虫的增殖增加。这表明寄生虫正从分化转向增殖。需要将无鞭毛体与ADPRT拮抗剂预孵育才能产生这种效应，这进一步证明蛋白质的ADP-核糖基化是利什曼原虫分化起始所必需的。
