KMID : 0606920150230010019
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Biomolecules & Therapeutics 2015 Volume.23 No. 1 p.19 ~ p.25
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Thymosin Beta-4, Actin-Sequestering Protein Regulates Vascular Endothelial Growth Factor Expression via Hypoxia-Inducible Nitric Oxide Production in HeLa Cervical Cancer Cells
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Ryu Yun-Kyoung
Lee Jae-Wook Moon Eun-Yi
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Abstract
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Vascular endothelial growth factor (VEGF) is an important regulator of neovascularization. Hypoxia inducible nitric oxide (NO) enhanced the expression of VEGF and thymosin beta-4 (T¥â4), actin sequestering protein. Here, we investigated whether NO-mediated VEGF expression could be regulated by T¥â4 expression in HeLa cervical cancer cells. Hypoxia inducible NO production and VEGF expression were reduced by small interference (si) RNA of T¥â4. Hypoxia response element (HRE)-luciferase activity and VEGF expression were increased by the treatment with N-(¥â-D-Glucopyranosyl)-N2-acetyl-S-nitroso-D, L-penicillaminamide (SNAP-1), to generate NO, which was inhibited by the inhibition of T¥â4 expression with T¥â4-siRNA. In hypoxic condition, HRE-luciferase activity and VEGF expression were inhibited by the treatment with NG-monomethyl-L-arginine (L-NMMA), an inhibitor to nitric oxide synthase (NOS), which is accompanied with a decrease in T¥â4 expression. VEGF expression inhibited by L-NMMA treatment was restored by the transfection with pCMV-T¥â4 plasmids for T¥â4 overexpression. Taken together, these results suggest that T¥â4 could be a regulator for the expression of VEGF via the maintenance of NOS activity.
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KEYWORD
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VEGF, Thymosin beta-4, Nitric oxide, Hypoxia, HIF-1¥á
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