A novel nucleic acid analogue shows strong angiogenic activity
A novel nucleic acid analogue shows strong angiogenic activity
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DOI：
10.1016/j.bbrc.2010.08.003
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发表时间：
2010-09-03
影响因子：
3.1
通讯作者：
Konishi, Ryoji
中科院分区：
文献类型：
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作者：
Tsukamoto, Ikuko;Sakakibara, Norikazu;Konishi, Ryoji
一种新的核酸类似物（2Cl-C.OXT-A）显著刺激人脐静脉内皮细胞（HUVEC）的管形成。其在100 μ M时的最大效力强于阳性对照血管内皮生长因子（VEGF）。在该浓度下，2Cl-C.OXT-A适度刺激HUVEC的增殖以及迁移。为了获得2Cl-C.OXT-A如何促进HUVEC中的血管生成应答的机制见解，我们使用磷酸特异性抗体作为探针进行免疫印迹分析。2Cl-C.OXT-A诱导MAP激酶ERK 1/2和上游MAP激酶MEK的稳健磷酸化/活化。相反，MEK抑制剂PD 98059消除了ERK 1/2激活和管形成，两者都被2Cl-C.OXT-A增强。相反，由2Cl-C.OXT-A引起的MAP激酶反应不被VEGF受体酪氨酸激酶的特异性抑制剂SU 5416抑制。总的来说，这些结果表明，2Cl-C.OXT-A-诱导HUVEC中由包含MEK和ERK 1/2的MAP激酶级联介导的血管生成反应，但不依赖于VEGF受体酪氨酸激酶。使用鸡绒毛尿囊膜（CAM）和兔角膜的体内测定也表明了2Cl-C.OXT-A的血管生成效力。(C)2010年爱思唯尔公司All rights reserved.
A novel nucleic acid analogue (2Cl-C.OXT-A) significantly stimulated tube formation of human umbilical endothelial cells (HUVEC). Its maximum potency at 100 mu M was stronger than that of vascular endothelial growth factor (VEGF), a positive control. At this concentration, 2Cl-C.OXT-A moderately stimulated proliferation as well as migration of HUVEC. To gain mechanistic insights how 2Cl-C.OXT-A promotes angiogenic responses in HUVEC, we performed immunoblot analyses using phospho-specific antibodies as probes. 2Cl-C.OXT-A induced robust phosphorylation/activation of MAP kinase ERK1/2 and an upstream MAP kinase kinase MEK. Conversely, a MEK inhibitor PD98059 abolished ERK1/2 activation and tube formation both enhanced by 2Cl-C.OXT-A. In contrast, MAP kinase responses elicited by 2Cl-C.OXT-A were not inhibited by SU5416, a specific inhibitor of VEGF receptor tyrosine kinase. Collectively these results suggest that 2Cl-C.OXT-A-induces angiogenic responses in HUVEC mediated by a MAP kinase cascade comprising MEK and ERK1/2, but independently of VEGF receptor tyrosine kinase. In vivo assay using chicken chorioallantoic membrane (CAM) and rabbit cornea also suggested the angiogenic potency of 2Cl-C.OXT-A. (C) 2010 Elsevier Inc. All rights reserved.