Levine L
Department of Biochemistry, Brandeis University Waltham, MA 02254.
Prostaglandins. 1991 Jun;41(6):615-24. doi: 10.1016/0090-6980(91)90066-o.
Preincubation of rat liver cells (the C-9 cell line) with okadaic acid (0.6 microM), a known inhibitor of protein-serine/threonine phosphate phosphatases 2A and 1, for 30 min amplified 6-keto-PGF1 alpha production stimulated by thapsigargin, thrombin, platelet activating factor (PAF), 12-O-tetradecanoylphorbol-13-acetate (TPA), the Ca2+ ionophore A-23187 and lysine-vasopressin (Lys.ADH) but not that stimulated by exogenous arachidonic acid. The amplification occurred within minutes after addition of the stimulators. The effect of preincubation was time dependent. Preincubation of the cells with okadaic acid (0.6 microM) for longer than 30 min decreased this amplification. The results suggest that inhibition of protein-serine/threonine phosphate phosphatase(s) can both positively and negatively regulate deesterification of phospholipids although the negative regulation may reflect a toxic response. Microcystin LR and nodularin, inhibitors of protein-serine/threonine phosphate phosphatases 2A and 1 in vitro, did not amplify 6-keto-PGF1 alpha production by PAF when incubated with intact cells.
用冈田酸（0.6微摩尔）对大鼠肝细胞（C - 9细胞系）进行预孵育30分钟，冈田酸是已知的蛋白丝氨酸/苏氨酸磷酸酶2A和1的抑制剂，可增强由毒胡萝卜素、凝血酶、血小板活化因子（PAF）、12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）、Ca2 +离子载体A - 23187和赖氨酸加压素（Lys.ADH）刺激产生的6 - 酮 - PGF1α，但不能增强由外源性花生四烯酸刺激产生的6 - 酮 - PGF1α。这种增强作用在加入刺激剂后的几分钟内就会出现。预孵育的效果具有时间依赖性。用冈田酸（0.6微摩尔）对细胞进行预孵育超过30分钟会降低这种增强作用。结果表明，抑制蛋白丝氨酸/苏氨酸磷酸酶可能对磷脂的去酯化作用产生正向和负向调节，尽管负向调节可能反映了一种毒性反应。微囊藻毒素LR和节球藻毒素是体外蛋白丝氨酸/苏氨酸磷酸酶2A和1的抑制剂，当与完整细胞一起孵育时，它们不会增强PAF刺激产生的6 - 酮 - PGF1α。
