Pesando D, Huitorel P, Dolcini V, Amade P, Girard J P
Laboratoire de Physiologie et Toxicologie Environnementales, EA 2138, Université de Nice -- Sophia Antipolis, France.
Eur J Cell Biol. 1998 Sep;77(1):19-26. doi: 10.1016/S0171-9335(98)80098-8.
Caulerpenyne (Cyn), the major secondary metabolite synthesized by the green alga Caulerpa taxifolia proliferating in the Mediterranean Sea, is a cytotoxic sesquiterpene. As this compound has an antiproliferative potency by inhibiting division of many types of cells, we examined the precise effects of Cyn during the early development of the sea urchin Paracentrotus lividus. Whereas Cyn (60 microM) had no effect on fertilization, it blocked the first cell division in the same manner whether added before or after fertilization, provided the drug was added before or during metaphase. Immunofluorescence localization revealed that Cyn had no effect on the microtubular sperm aster formation, pronuclei migration and fusion, chromosome condensation, nuclear envelope breakdown, and bipolar mitotic spindle assembly. However, mitosis was blocked in a metaphase-like stage at which most chromosomes were aligned at the equatorial plate, while a few of them had not even migrated towards the metaphase plate. When added after the metaphase-anaphase transition, the first division occurred normally but the second division was inhibited with the same phenotype as described above. We previously showed that Cyn did not affect protein synthesis or H1 kinase activation or deactivation (Pesando et al., 1996, Aquat. Toxicol. 35, 139), but that it partially inhibited DNA synthesis. Our results establish that Cyn does not affect the microfilament-dependent processes of fertilization and cytokinesis and allows the beginning of mitosis, but prevents normal DNA replication and results in metaphase-like arrest of sea urchin embryos.
刺尾鱼毒素(Cyn)是在地中海大量繁殖的绿藻——杉叶蕨藻合成的主要次生代谢产物,是一种具有细胞毒性的倍半萜烯。由于该化合物通过抑制多种细胞分裂具有抗增殖能力,我们研究了刺尾鱼毒素在海胆Paracentrotus lividus早期发育过程中的精确作用。虽然刺尾鱼毒素(60微摩尔)对受精没有影响,但无论在受精前还是受精后添加,只要在中期前或中期添加该药物,它都会以相同的方式阻断第一次细胞分裂。免疫荧光定位显示,刺尾鱼毒素对微管精子星体形成、原核迁移和融合、染色体浓缩、核膜破裂以及双极有丝分裂纺锤体组装没有影响。然而,有丝分裂在类似中期的阶段被阻断,此时大多数染色体排列在赤道板上,而其中一些甚至尚未向中期板迁移。当在中期 - 后期转换后添加时,第一次分裂正常发生,但第二次分裂受到抑制,其表型与上述相同。我们之前表明,刺尾鱼毒素不影响蛋白质合成或H1激酶的激活或失活(Pesando等人,1996年,《水生毒理学》35卷,第139页),但它部分抑制DNA合成。我们的结果表明,刺尾鱼毒素不影响受精和胞质分裂中依赖微丝的过程,并允许有丝分裂开始,但会阻止正常的DNA复制,并导致海胆胚胎出现类似中期的停滞。