A novel nucleic acid analogue shows strong angiogenic activity

作者：Tsukamoto Ikuko^*; Sakakibara Norikazu; Maruyama Tokumi; Igarashi Junsuke; Kosaka Hiroaki; Kubota Yasuo; Tokuda Masaaki; Ashino Hiromi; Hattori Kenichi; Tanaka Shinji; Kawata Mitsuhiro; Konishi Ryoji

来源：Biochemical and Biophysical Research Communications, 2010, 399(4): 699-704.

DOI：10.1016/j.bbrc.2010.08.003

• Angiogenesis stimulator
• Tube formation
• HUVEC
• Nucleic acid analogue
• ERK1/2 activation
• MAP kinase cascade
• Chorioallantoic membrane assay
• Corneal micropocket assay

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.

• 出版日期2010-9-3
• 单位河北医科大学