Marine compound catunaregin inhibits angiogenesis through the modulation of phosphorylation of akt and eNOS in vivo and in vitro.

Marine compound catunaregin inhibits angiogenesis through the modulation of phosphorylation of akt and eNOS in vivo and in vitro.
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海洋化合物 Catunaregin 通过体内外调节 Akt 和 eNOS 磷酸化抑制血管生成

DOI:
10.3390/md12052790
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发表时间:
2014-05-12
期刊:
影响因子:
5.4
通讯作者:
Yao SZ
Yao SZ
中科院分区:
医学2区
文献类型:
--
作者:
Liu JX;Luo MQ;Xia M;Wu Q;Long SM;Hu Y;Gao GC;Yao XL;He M;Su H;Luo XM;Yao SZ

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血管生成是从预先存在的脉管系统形成血管。过度或不受控制的血管生成是许多病理状况的主要原因,而抑制异常血管生成对于患有病理性血管生成的患者是有益的。 Catunaregin 是从红树林中分离出来的新型海洋化合物的核心。在人脐静脉内皮细胞 (HUVEC) 和斑马鱼中研究了 catunaregin 的潜在抗血管生成作用。在存在或不存在 VEGF 的情况下,用不同浓度的 catunaregin 处理 HUVEC。在 HUVEC 中用卡杜雷金处理后,评估了血管生成表型,包括细胞侵袭、细胞迁移和管形成。使用蛋白质印迹法探讨了 AKT、eNOS 和 ERK1/2 在 catunaregin 诱导的抗血管生成中的可能参与。在斑马鱼胚胎新生血管和尾鳍再生试验中进一步测试了卡杜雷金的抗血管生成作用。我们发现,在 HUVEC 和斑马鱼胚胎新生血管形成以及斑马鱼尾鳍再生测定中,catunaregin 剂量依赖性地抑制血管生成。此外,catunaregin 显着降低 Akt 和 eNOS 的磷酸化,但不降低 ERK1/2 的磷酸化。目前的工作表明,catunaregin 至少部分通过调节 Akt 和 eNOS 信号通路发挥抗血管生成活性。
Angiogenesis is the formation of blood vessels from pre-existing vasculature. Excessive or uncontrolled angiogenesis is a major contributor to many pathological conditions whereas inhibition of aberrant angiogenesis is beneficial to patients with pathological angiogenesis. Catunaregin is a core of novel marine compound isolated from mangrove associate. The potential anti-angiogenesis of catunaregin was investigated in human umbilical vein endothelial cells (HUVECs) and zebrafish. HUVECs were treated with different concentrations of catunaregin in the presence or absence of VEGF. The angiogenic phenotypes including cell invasion cell migration and tube formation were evaluated following catunaregin treatment in HUVECs. The possible involvement of AKT, eNOS and ERK1/2 in catunaregin-induced anti-angiogenesis was explored using Western blotting. The anti-angiogenesis of catunaregin was further tested in the zebrafish embryo neovascularization and caudal fin regeneration assays. We found that catunaregin dose-dependently inhibited angiogenesis in both HUVECs and zebrafish embryo neovascularization and zebrafish caudal fin regeneration assays. In addition, catunaregin significantly decreased the phosphorylation of Akt and eNOS, but not the phosphorylation of ERK1/2. The present work demonstrates that catunaregin exerts the anti-angiogenic activity at least in part through the regulation of the Akt and eNOS signaling pathways.
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