Involvement of SAPK/JNK in prostaglandin E1-induced VEGF synthesis in osteoblast-like cells
Involvement of SAPK/JNK in prostaglandin E1-induced VEGF synthesis in osteoblast-like cells
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DOI：
10.1016/j.mce.2004.03.010
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发表时间：
2004-05-31
影响因子：
4.1
通讯作者：
Kozawa, O
中科院分区：
文献类型：
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作者：
Kanno, Y;Tokuda, H;Kozawa, O
我们先前报道前列腺素E-1(PGE(1))通过cAMP依赖的蛋白激酶激活成骨样MC3T3-E1细胞中的p44/p42丝裂原激活蛋白(MAP)和p38 MAP，而p38 MAP而不是P42/P44 MAP参与了PGE(1)诱导的血管内皮生长因子(VEGF)的合成。在本研究中，我们探讨了应激激活蛋白激酶/c-jun氨基末端激酶(SAPK/JNK)在前列腺素E(1)诱导MC3T3-E1细胞合成血管内皮生长因子中的作用。PGE(1)可诱导SAPK/JNK的磷酸化。SAPK/JNK的特异性抑制剂SP600125可显著抑制PGE(1)诱导的血管内皮生长因子的合成。腺苷环化酶的直接激活剂Forsklin可诱导SAPK/JNK的磷酸化，质膜通透性cAMP类似物刺激的8溴cAMP可显著降低SP600125刺激的血管内皮生长因子的合成。SP600125可抑制PGE(1)诱导的SAPK/JNK的磷酸化，但不影响PGE(1)诱导的p38 MAPK的磷酸化。SP600125对PGE(1)诱导的c-jun磷酸化也有抑制作用。P38MAPK抑制剂SB203580不能降低PGE(1)诱导的SAPK/JNK的磷酸化。SP600125和SB203580联合应用可相加抑制PGE(1)刺激的血管内皮生长因子的合成。这些结果有力地提示PGE(1)激活成骨细胞SAPK/JNK，SAPK/JNK参与PGE(1)诱导的血管内皮生长因子的合成。(C)2004爱思唯尔爱尔兰有限公司。保留所有权利。
We previously reported that prostaglandin E-1 (PGE(1)) activates both p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase via cAMP-dependent protein kinase in osteoblast-like MC3T3-E1 cells, and that p38 MAP kinase but not p42/p44 MAP kinase is involved in PGE(1)-induced synthesis of vascular endothelial growth factor (VEGF). In the present study, we investigated the involvement of stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in the PGE(1)-induced VEGF synthesis in MC3T3-E1 cells. PGE(1) induced the phosphorylation of SAPK/JNK. SP600125, a specific inhibitor of SAPK/JNK, markedly reduced the PGE(1)-induced VEGF synthesis. Forskolin, a direct activator of adenylyl cyclase, elicited the phosphorylation of SAPK/JNK, and 8bromo-cAMP, a plasma membrane-permeable cAMP analogue-stimulated VEGF synthesis was significantly reduced by SP600125. SP600125 suppressed the PGE(1)-induced phosphorylation of SAPK/JNK without affecting the phosphorylation of p38 MAP kinase induced by PGE(1). The phosphorylation of c-Jun induced by PGE(1) was also inhibited by SP600125. SB203580, a p38 MAP kinase inhibitor, failed to reduce the PGE(1) induced phosphorylation of SAPK/JNK. A combination of SP600125 and SB203580 suppressed the PGE(1)-stimulated VEGF synthesis in an additive manner. These results strongly suggest that PGE(1) activates SAPK/JNK in osteoblasts, and that SAPK/JNK plays a part in PGE(1)-induced VEGF synthesis. (C) 2004 Elsevier Ireland Ltd. All rights reserved.