Yoshizawa S, Matsushima R, Watanabe M F, Harada K, Ichihara A, Carmichael W W, Fujiki H
Cancer Prevention Division, National Cancer Center Research Institute, Tokyo, Japan.
J Cancer Res Clin Oncol. 1990;116(6):609-14. doi: 10.1007/BF01637082.
Microcystins and nodularin, isolated from toxic blue-green algae, are hepatotoxic monocyclic polypeptides. Both microcystins and nodularin inhibited in vitro protein phosphatase activity present in a cytosolic fraction of mouse liver, bound to the okadaic acid receptors, protein phosphatases 1 and 2A, and thus resulted in the increase of phosphoproteins; this was referred to as the apparent "activation" of protein kinases. Their concentrations causing 50% of the maximal effects are comparable to that of okadaic acid, a potent protein phosphatase inhibitor and a potent tumor promoter, in the nanomolar range of concentration. The increase of phosphoproteins was observed in rat primary cultured hepatocytes and was subsequently associated with morphological changes, which appeared to be a step in the process of hepatotoxicity. The well-known hepatotoxic compounds, alpha-amanitin and phalloidin, did not show any effects similar to those of microcystins, nodularin and okadaic acid. It is suggested that the hepatotoxicity of microcystins and nodularin may result from inhibition of protein phosphatases and the increase of phosphoproteins.
从有毒蓝藻中分离出的微囊藻毒素和节球藻毒素是具有肝毒性的单环多肽。微囊藻毒素和节球藻毒素均能在体外抑制小鼠肝脏胞质部分中存在的、与冈田酸受体（蛋白磷酸酶1和2A）结合的蛋白磷酸酶活性，从而导致磷酸化蛋白增加；这被称为蛋白激酶的表观“激活”。它们产生最大效应50%时的浓度与冈田酸（一种强效蛋白磷酸酶抑制剂和强效肿瘤促进剂）在纳摩尔浓度范围内的浓度相当。在大鼠原代培养肝细胞中观察到磷酸化蛋白增加，随后出现形态学变化，这似乎是肝毒性过程中的一个步骤。著名的肝毒性化合物α-鹅膏毒肽和鬼笔环肽未表现出与微囊藻毒素、节球藻毒素和冈田酸类似的任何效应。有人提出，微囊藻毒素和节球藻毒素的肝毒性可能是由于蛋白磷酸酶的抑制和磷酸化蛋白的增加所致。
