Kawamoto F, Fujioka H, Murakami R, Hagiwara M, Ishikawa T, Hidaka H
Department of Medical Zoology, Nagoya University School of Medicine, Japan.
Eur J Cell Biol. 1993 Feb;60(1):101-7.
The induction mechanism of gamete formation (gametogenesis) in a rodent malaria parasite, Plasmodium berghei, was investigated using Ca2+ antagonists, protein kinase inhibitors and amiloride, an inhibitor of monovalent cation/H+ exchange. Treatment with 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8, a Ca2+ release inhibitor) and W-7/W-66 (calmodulin inhibitors) blocked formation of male gametes by inhibiting DNA synthesis from 1.5C to 8C level. In contrast, inhibitors of cAMP/cGMP-dependent protein kinases such as H-8, H-87, H-89 and staurosporine also ceased the development of gametocytes, but DNA synthesis in male gametocytes occurred as in the controls. Electron microscopy revealed that male gametocytes treated with TMB-8 and W-7 failed to enlarge nuclei and to form axonemes in the cytoplasm. In female gametocytes, treatment with both Ca2+ antagonists resulted in a dramatic morphological change in the endoplasmic reticulum (ER), which is thought to be a Ca2+ store. The ER network condensed near nuclei and was laminated by the abnormal attachment of ribosomes between two ER membranes. On the other hand, male gametocytes treated with protein kinase inhibitors or amiloride had enlarged nuclei and axonemes, but failed to develop further. The ER network in female gametocytes treated with these inhibitors was similar to that in the controls.
利用钙离子拮抗剂、蛋白激酶抑制剂和一价阳离子/氢离子交换抑制剂阿米洛利，对啮齿动物疟原虫伯氏疟原虫配子形成（配子发生）的诱导机制进行了研究。用3,4,5-三甲氧基苯甲酸8-（二乙氨基）辛酯（TMB-8，一种钙离子释放抑制剂）和W-7/W-66（钙调蛋白抑制剂）处理，通过抑制从1.5C到8C水平的DNA合成来阻断雄配子的形成。相比之下，cAMP/cGMP依赖性蛋白激酶抑制剂，如H-8、H-87、H-89和星形孢菌素，也会使配子细胞的发育停止，但雄配子细胞中的DNA合成与对照相同。电子显微镜显示，用TMB-8和W-7处理的雄配子细胞未能使细胞核增大，也未能在细胞质中形成轴丝。在雌配子细胞中，用两种钙离子拮抗剂处理导致内质网（ER）出现显著的形态变化，内质网被认为是钙离子储存库。内质网网络在细胞核附近浓缩，并因核糖体异常附着在两个内质网膜之间而分层。另一方面，用蛋白激酶抑制剂或阿米洛利处理的雄配子细胞细胞核和轴丝增大，但未能进一步发育。用这些抑制剂处理的雌配子细胞中的内质网网络与对照相似。
