Selective inhibition of cytokinesis in sea urchin embryos by the marine natural product pseudopterolide.
Low concentrations (1-10 microM) of the marine natural product pseudopterolide inhibited cytokinesis and induced formation of multinucleate cells in fertilized Strongylocentrotus purpuratus embryos. As determined by immunofluorescence microscopy using fluorescent stains for actin filaments, microtubules, and chromosomes, pseudopterolide inhibited cytokinesis selectively by disrupting the contractile ring, whereas spindle microtubule organization and mitotic chromosome segregation to opposite spindle poles were unimpaired. At somewhat higher concentrations (16-20 microM), pseudopterolide induced formation of microtubule spiral asters, which are believed to be caused by rotation of the cytoplasm relative to the cell cortex. The effects of pseudopterolide on cytokinesis were cell-cycle dependent. The actions of pseudopterolide in fertilized sea urchin embryos were strikingly similar to the actions of another marine natural product, stypoldione, a structurally unrelated orthoquinone that reacts covalently with the sulfhydryl groups of glutathione, beta-mercaptoethanol, cysteine, and a number of proteins [Mol. Pharmacol. 35:635-642 (1989)]. In the present study, pseudopterolide was also found to react with sulfhydryl groups of glutathione, beta-mercaptoethanol, and cysteine. The results indicate that the cellular target for pseudopterolide, like the target for stypoldione, may be an especially sensitive sulfhydryl-containing protein involved in the formation or function of the contractile ring.
Grace
K J
KJ
Department of Biological Sciences, University of California, Santa Barbara 93106.
Medina
M
M
Jacobs
R S
RS
Wilson
L
L
D000199:Actins / Q000187:drug effects; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000187:drug effects; D007783:Lactones / Q000378:metabolism / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D008938:Mitosis / Q000187:drug effects*; D011809:Quinones / Q000378:metabolism / Q000494:pharmacology; D012617:Sea Urchins; D013438:Sulfhydryl Compounds / Q000378:metabolism
D000199:Actins; D007783:Lactones; D011809:Quinones; D013438:Sulfhydryl Compounds; C039754:stypoldione; C074182:pseudopterolide