Affiliation:
1. Department of Biochemistry, Kyushu Unviersity School of Medicine, Fukuoka, Japan.
Abstract
Oxygen radicals are induced under various pathologic conditions associated with neovascularization. Oxygen radicals modulate angiogenesis in cultured human microvascular endothelial cells by an unknown mechanism. Treatment of human microvascular endothelial cells for 15 min with 0.1 to 0.5 mM hydrogen peroxide (H2O2) or 100 U of tumor necrosis factor alpha per ml induced tubular morphogenesis in type I collagen gels. Gel shift assays with nuclear extracts demonstrated that H2O2 increases the binding activities of two transcription factors, NF-kappaB and AP-1, but not of Spl. Tumor necrosis factor alpha increased the binding activities of all three factors. A supershift assay with specific antibodies against JunB, JunD, and c-Jun (Jun family) showed that the antibody against c-Jun supershifted the AP-1 complex after H2O2 treatment. Coadministration of the antisense sequence of NF-kappaB inhibited H2O2-dependent tubular morphogenesis, and the antisense c-Jun oligonucleotide caused partial inhibition. The angiogenic factor responsible for H2O2-induced tubular morphogenesis was examined. Cellular mRNA levels of vascular endothelial growth factor and interleukin-8 (IL-8), but not those of transforming growth factor alpha, were increased after treatment with 0.5 mM H2O2. Coadministration of anti-IL-8 antibody inhibited tubular morphogenesis enhanced by H2O2, and IL-8 itself also enhanced the formation of tube-like structures. Treatment with antisense NF-kappaB oligonucleotide completely blocked H2O2-dependent IL-8 production by endothelial cells. The tubular morphogenesis of vascular endothelial cells after treatment with oxidative stimuli and its possible association with NF-kappaB and IL-8, is examined.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
Reference63 articles.
1. Induction of vascular endothelial tubular morphogenesis by human glioma cells: a model system for tumor angiogenesis;Abe T.;J. Clin. Invest.,1993
2. The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation;Angel P.;Biochim. Biophys. Acta,1991
3. The exogenous control of transfected c-fos gene expression and angiogenesis in cells implanted into the rat brain;Asakuno K.;Brain Res.,1995
4. The inducible transcription activator NF-~B: regulation by distinct protein subunits;Baeuerle P. A.;Biochem. Biophys. Res. Commun.,1991
5. Tumor vascular permeability factor stimulates endothelial cell growth and angiogenesis;Connolly D. T.;J. Clin. Invest.,1989
Cited by
212 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献