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有读书笔记Inhibition of mitosis by okadaic acid: possible involvement of a protein phosphatase 2A in the transition from metaphase to anaphase

阿平 添加于 2012-5-5 06:13 | 1846 次阅读 | 0 个评论

  •  作 者

    Vandre DD, Wills VL

  •  摘 要

    The effects of the protein phosphatase inhibitor okadaic acid were examined using the pig kidney cell line LLC-PK. At relatively low concentrations of the inhibitor (8-40 nM), cells became blocked in a metaphase-like mitotic state beginning 6-8 h after initial treatment. Spindle microtubules were present throughout the period of the mitotic block, but were not stabilized since they remained sensitive to nocodazole depolymerization. With increasing length of the mitotic block chromosome alignment at the metaphase plate was disrupted and multipolar spindles developed. Cells continued to accumulate in mitosis for at least 24 h, indicating that at these low concentrations okadaic acid was not cytotoxic, but rather acted as a cytostatic agent. Upon release of the okadaic acid block, mitotic LLC-PK cells recovered and completed anaphase. After extended periods of treatment some cells were able to escape the okadaic acid-induced mitotic block. These cells were multinucleate and had undergone cytokinesis in the absence of chromosome segregation. At higher concentrations of okadaic acid (0.5-1.0 microM), mitosis was blocked within 30-60 min of treatment. However, within 90-120 min treated cells rounded up and detached from the monolayer, regardless of whether they were in interphase or mitosis. Cytoplasmic microtubules were depolymerized in the detached cells, and these cells could not recover from the cytotoxic effects of such high concentrations of okadaic acid. Thus, differential effects of the phosphatase inhibitor could be demonstrated, depending upon the concentration of okadaic acid applied to the cultures. The okadaic acid-induced mitotic blockage was probably due to the inhibition of a type 2A protein phosphatase that is involved in the transition from metaphase to anaphase.

  •  详细资料

    • 关键词: Anaphase; Animals; Cell Line/cytology/drug effects; Cell Survival/drug effects; DNA/analysis; Ethers, Cyclic/*pharmacology; Metaphase/drug effects; Microtubules/*drug effects; Mitosis/*drug effects; Mitotic Spindle Apparatus/*drug effects; Okadaic Acid; Phosphoprotein Phosphatases/*antagonists & inhibitors; Protein Phosphatase 2; Swine
    • 文献种类: Journal Article
    • 期刊名称: Journal of Cell Science
    • 期刊缩写: J Cell Sci
    • 期卷页: 1992年  第101 ( Pt 1)卷 79-91页
    • 地址: Department of Cell Biology, Ohio State University, Columbus 43210
    • ISBN: 0021-9533

  • 学科领域 生物医药 » 生物学

  •  标 签

    PP1  PP2A 

  • 相关链接  URL 

  •  阿平 的文献笔记  订阅

    OA 可以说是蛋白磷酸酶领域被用得最多也可说是用得最滥的药物了
    其in vito对PP2A IC50 0.1nM,对PP1 1nM，虽然能够穿过细胞膜，但是要使胞内达到保外浓度，需要很长时间，比如这篇文章用40nM要6-8小时才会起效去抑制PP2A.而使用高浓度1uM到10uM，最然能够在1小时内起效，但是细胞已经撑不住都死亡了，所以非常难以控制。
    这药用得好，救人，用不好，害死人呀
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