Abstract
We have previously shown that prostaglandin E(1) (PGE(1)) stimulates the synthesis of vascular endothelial growth factor (VEGF) through p38 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) but not p44/p42 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of Rho-kinase in the PGE(1)-stimulated VEGF synthesis in these cells. PGE(1) induced within 3min the phosphorylation of myosin phosphatase targeting subunit (MYPT-1), a substrate of Rho-kinase. Y27632 and fasudil, specific inhibitors of Rho-kinase, which attenuated the MYPT-1 phosphorylation, significantly suppressed the PGE(1)-stimulated VEGF synthesis. Y27632 and fasudil markedly reduced the PGE(1)-induced phosphorylation of SAPK/JNK without affecting the phosphorylation levels of p38 MAP kinase or p44/p42 MAP kinase. These results strongly suggest that Rho-kinase functions at a point upstream of SAPK/JNK and regulates PGE(1)-stimulated VEGF synthesis in osteoblasts.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
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3T3 Cells
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Alprostadil / pharmacology*
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Amides / pharmacology
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Animals
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Cell Line
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JNK Mitogen-Activated Protein Kinases / metabolism*
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Mice
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / metabolism
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Myosin-Light-Chain Kinase / metabolism
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Myosin-Light-Chain Phosphatase
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Osteoblasts / cytology*
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Phosphorylation / drug effects
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Pyridines / pharmacology
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Vascular Endothelial Growth Factor A / biosynthesis*
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p38 Mitogen-Activated Protein Kinases / metabolism
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rho-Associated Kinases / metabolism*
Substances
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Amides
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Pyridines
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Vascular Endothelial Growth Factor A
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Y 27632
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
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rho-Associated Kinases
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Myosin-Light-Chain Kinase
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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p38 Mitogen-Activated Protein Kinases
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Myosin-Light-Chain Phosphatase
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Ppp1r12a protein, mouse
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Alprostadil
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fasudil