HEPATOCYTE DEFORMATION INDUCED BY CYANOBACTERIAL TOXINS REFLECTS INHIBITION OF PROTEIN PHOSPHATASES
HEPATOCYTE DEFORMATION INDUCED BY CYANOBACTERIAL TOXINS REFLECTS INHIBITION OF PROTEIN PHOSPHATASES
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DOI：
10.1016/s0006-291x(05)80936-2
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发表时间：
1990-12-31
影响因子：
3.1
通讯作者：
HARTSHORNE, D
中科院分区：
文献类型：
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作者：
ERIKSSON, JE;TOIVOLA, D;HARTSHORNE, D
环肽肝毒素微囊藻毒素-LR、7-去甲基-微囊藻毒素-RR 和结球菌素是 1 型和 2A 型蛋白磷酸酶的有效抑制剂。它们的抑制效力类似于花萼蛋白-A，并且在较小程度上类似于冈田酸。这些肝毒素会增加肝细胞中蛋白质磷酸化的总体水平。有证据表明，肝细胞中的形态变化和对细胞骨架的影响是由于磷酸酶抑制所致。这些化合物诱导肝细胞变形的效力与其抑制磷酸酶活性的效力相似。这些结果表明这些肽的肝毒性与磷酸酶的抑制有关，并进一步表明蛋白质磷酸化在维持这些细胞的结构和稳态完整性中的重要性。
The cyclic peptide hepatotoxins microcystin-LR, 7-desmethyl-microcystin-RR and nodularin are potent inhibitors of the protein phosphatases type 1 and type 2A. Their potency of inhibition resembles calyculin-A and to a lesser extent okadaic acid. These hepatotoxins increase the overall level of protein phosphorylation in hepatocytes. Evidence is presented to indicate that in hepatocytes the morphological changes and effects on the cytoskeleton are due to phosphatase inhibition. The potency of these compounds in inducing hepatocyte deformation is similar to their potency in inhibiting phosphatase activity. These results suggest that the hepatotoxicity of these peptides is related to inhibition of phosphatases, and further indicate the importance of the protein phosphorylation in maintenance of structural and homeostatic integrity in these cells.