Angiostatin Inhibition of Vascular Endothelial Growth Factor- Stimulated Nitric Oxide Production in Endothelial Cells
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- Takahashi Satoru
- First Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan
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- Shinya Tomohiro
- First Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan
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- Sugiyama Akinori
- First Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Japan Department of Health Chemistry, School of Pharmaceutical Sciences, Iwate Medical University, Japan
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Angiostatin (AS), a proteolytic fragment of plasminogen, is a potent antiangiogenic factor. It was reported that AS attenuates the vasodilatory response to vascular endothelial growth factor (VEGF) in isolated interventricular arterioles. Here, we investigated the effect of AS on nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs). AS inhibited VEGF-stimulated NO production in a dose-dependent manner, whereas AS alone did not affect basal NO production. Disruption of kringle structures by reduction of disulfide bonds resulted in the loss of the inhibitory effect of AS on VEGF-stimulated NO production. To elucidate how AS might impair VEGF activation of endothelial NO synthase (eNOS), we further examined whether AS would affect Ca2+-dependent and -independent pathways of eNOS activation. AS had no effect on the transient increase in cytosolic Ca2+ levels elicited by VEGF. In contrast, AS prevented VEGF-potentiated eNOS phosphorylation at Ser1177. These results clearly indicate that AS inhibits VEGF-stimulated NO production in HUVECs without affecting basal NO production. The kringle structures of AS are required for this effect, and impairment of Ser1177 phosphorylation of eNOS might be involved in the inhibition of VEGF-stimulated NO production by AS.
収録刊行物
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- Journal of Pharmacological Sciences
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Journal of Pharmacological Sciences 112 (4), 432-437, 2010
公益社団法人 日本薬理学会
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詳細情報 詳細情報について
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- CRID
- 1390001205180425600
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- NII論文ID
- 10027909085
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- NII書誌ID
- AA11806667
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- ISSN
- 13478648
- 13478613
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- NDL書誌ID
- 10651063
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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