Ito Y, Suzuki A, Watanabe-Tomita Y, Oiso Y, Kozawa O
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Prostaglandins Leukot Essent Fatty Acids. 1996 Nov;55(5):357-61. doi: 10.1016/s0952-3278(96)90042-3.
We examined the effect of okadaic acid, an inhibitor of protein phosphatase type 1 and 2A, on prostaglandin E1 (PGE1)-induced alkaline phosphatase (ALP) activity in osteoblast-like MC3T3-E1 cells. PGE1 increased ALP activity dose dependently in the range between 10 nM and 0.3 microM in these cells. The pretreatment with okadaic acid enhanced the PGE1-induced ALP activity in a dose-dependent manner in the range between 0.1 and 5 nM. On the other hand, 1-norokadaone, a less potent analogue of okadaic acid, had no effect on the PGE1-induced ALP activity. Tautomycin, an another inhibitor of protein phosphatase type 1 and 2A, also enhanced the PGE1-induced ALP activity. PGE1 stimulated cAMP accumulation dose dependently in the range between 10 nM and 0.3 microM. However, PGE1 had no effect on the formation of inositol phosphates. Okadaic acid did not affect the PGE1-induced cAMP accumulation. Okadaic acid dose dependently enhanced the dibutyryl cAMP-induced ALP activity. These results strongly suggest that protein phosphatase type 1 and/or 2A act as a regulator of ALP activity at a point downstream from protein kinase A in osteoblast-like cells.
我们研究了蛋白磷酸酶1型和2A型的抑制剂冈田酸对前列腺素E1（PGE1）诱导的成骨样MC3T3-E1细胞中碱性磷酸酶（ALP）活性的影响。在这些细胞中，PGE1在10 nM至0.3 μM的范围内剂量依赖性地增加了ALP活性。用冈田酸预处理在0.1至5 nM的范围内以剂量依赖性方式增强了PGE1诱导的ALP活性。另一方面，冈田酸的一种活性较低的类似物1-去甲冈田酮对PGE1诱导的ALP活性没有影响。另一蛋白磷酸酶1型和2A型的抑制剂 tautomycin也增强了PGE1诱导的ALP活性。PGE1在10 nM至0.3 μM的范围内剂量依赖性地刺激了cAMP积累。然而，PGE1对肌醇磷酸的形成没有影响。冈田酸不影响PGE1诱导的cAMP积累。冈田酸剂量依赖性地增强了二丁酰cAMP诱导的ALP活性。这些结果有力地表明，在成骨样细胞中，蛋白磷酸酶1型和/或2A型在蛋白激酶A下游的某个点作为ALP活性的调节剂发挥作用。
