Runnegar M T, Kong S, Berndt N
Department of Medicine, Children's Hospital, Los Angeles, California.
Am J Physiol. 1993 Aug;265(2 Pt 1):G224-30. doi: 10.1152/ajpgi.1993.265.2.G224.
Administration of microcystin (MCYST)-YM or -LR (peptide hepatotoxins produced by the cyanobacterium Microcystis aeruginosa) to mice resulted in the inhibition of liver protein phosphatase 1 and 2A activity. In all cases significant inhibition preceded or accompanied clinical changes due to MCYST intoxication. Fifteen minutes after intraperitoneal injection of lethal doses of MCYST-YM protein phosphatase activity was already decreased to 44% of controls, and by 60 min was further decreased to 22% of controls. The inhibition was dose dependent: intraperitoneal injection with 84 nmol/kg of MCYST-YM and 48 nmol/kg of MCYST-LR were the minimum doses required for significant inhibition at 60 min. Pretreatment of mice with 200 mumol/kg of rifamycin prevented the inhibition of liver protein phosphatase. The inhibition was tissue specific, with none detected in the kidneys, an organ that, unlike the liver, does not accumulate MCYST. In contrast to MCYST intoxication, lethal doses of phalloidin, a peptide hepatotoxin that produces clinical and pathological changes similar to MCYST, did not cause any inhibition of protein phosphatases.
给小鼠施用微囊藻毒素（MCYST）-YM 或 -LR（由铜绿微囊藻产生的肽类肝毒素）会导致肝脏蛋白磷酸酶 1 和 2A 的活性受到抑制。在所有情况下，显著的抑制作用先于或伴随因微囊藻毒素中毒引起的临床变化出现。腹腔注射致死剂量的 MCYST-YM 后 15 分钟，蛋白磷酸酶活性已降至对照组的 44%，到 60 分钟时进一步降至对照组的 22%。这种抑制作用呈剂量依赖性：腹腔注射 84 nmol/kg 的 MCYST-YM 和 48 nmol/kg 的 MCYST-LR 是在 60 分钟时产生显著抑制所需的最小剂量。用 200 μmol/kg 的利福平预处理小鼠可防止肝脏蛋白磷酸酶受到抑制。这种抑制作用具有组织特异性，在肾脏中未检测到，肾脏是一个与肝脏不同、不会积累微囊藻毒素的器官。与微囊藻毒素中毒不同，致死剂量的鬼笔环肽（一种产生与微囊藻毒素相似的临床和病理变化的肽类肝毒素）不会引起蛋白磷酸酶的任何抑制。
