Oida K, Maeda H, Kohno M, Nakai T, Horie S, Ishii H
Third Department of Internal Medicine, Fukui Medical School, Japan.
Thromb Res. 1997 Feb 1;85(3):169-76. doi: 10.1016/s0049-3848(97)00001-7.
We examined the effects of okadaic acid, a potent specific inhibitor of protein phosphatases 1 and 2A, on the expression of thrombomodulin (TM), a cell surface anti-thrombotic glycoprotein, on cultured human umbilical endothelial cells. Okadaic acid (2.5-10 nM) significantly increased TM antigen levels in parallel with its cofactor activity for thrombin-dependent protein C activation. Incubation of cells with 10 nM okadaic acid for 18 h induced an approximately 240% up-regulation of TM antigen levels that was accompanied by an increase in TM mRNA levels. Co-incubation of cells with okadaic acid and dibutyryl cyclic AMP further increased TM antigen levels. Furthermore, the effect of cAMP on TM expression was augmented by the pretreatment of cells with 10 nM okadaic acid for 18 h. These results provide evidence for the involvement of protein phosphatase in the cellular regulatory mechanisms for TM expression, which is distinct from that by cAMP.
我们研究了冈田酸（一种蛋白磷酸酶1和2A的强效特异性抑制剂）对培养的人脐静脉内皮细胞上血栓调节蛋白（TM，一种细胞表面抗血栓糖蛋白）表达的影响。冈田酸（2.5 - 10 nM）显著增加了TM抗原水平，同时其对凝血酶依赖性蛋白C激活的辅因子活性也增加。用10 nM冈田酸处理细胞18小时可诱导TM抗原水平上调约240%，同时TM mRNA水平也增加。将细胞与冈田酸和二丁酰环磷酸腺苷共同孵育可进一步增加TM抗原水平。此外，用10 nM冈田酸预处理细胞18小时可增强环磷酸腺苷对TM表达的影响。这些结果为蛋白磷酸酶参与TM表达的细胞调节机制提供了证据，这与环磷酸腺苷的作用机制不同。
