Abstract
(R,R)ZX-5 is a NO regulatory compound, which could significantly increase choroidal blood flow in New Zealand rabbit. The aim of this paper is to investigate the molecular mechanism of (R,R)ZX-5 promoting NO production. Besides this, we also investigated the antiangiogenic activity of (R,R)ZX-5. Analysis of Western blot showed that (R,R)ZX-5 up-regulated the expression of Akt, p-Akt (Thr473), eNOS and p-eNOS (Ser1177), down-regulated the expression of Cyclin D1 in human retinal endothelial cells and escalated the intracellular free Ca(2+) concentration. Additionally, (R,R)ZX-5 inhibited the growth of blood vessels in the chick chorioallantoic membrane model. It is concluded that (R,R)ZX-5 promotes choroidal blood flow through PI3K/Akt-eNOS and Akt-Ca(2+)-eNOS pathways. Additionally, (R,R)ZX-5 can inhibit angiogenesis.
Keywords:
(R,R)ZX-5; age-related macular degeneration; angiogenesis; choroidal neovascularization; signal pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Angiogenesis Inhibitors / pharmacology*
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Aniline Compounds / metabolism
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Animals
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Blotting, Western
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Calcium / metabolism
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Cell Line
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Chick Embryo
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Chorioallantoic Membrane / drug effects
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Chorioallantoic Membrane / metabolism
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Choroid / blood supply
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Choroid / drug effects
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Cyclin D1 / metabolism
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Endothelial Cells / drug effects
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Endothelial Cells / metabolism
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Humans
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Intracellular Space / drug effects
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Intracellular Space / metabolism
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Nitric Oxide / biosynthesis*
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Nitric Oxide Synthase Type III / metabolism
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Phosphorylation / drug effects
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Proto-Oncogene Proteins c-akt / metabolism
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Rabbits
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Thiourea / analogs & derivatives*
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Thiourea / pharmacology*
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Xanthenes / metabolism
Substances
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1-phenyl-3-(3-methoxy-2-propoxy-5-(4-(3,4,5-trimethoxyphenyl)-1,3-dithiolane-2-yl)phenyl)thiourea
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Angiogenesis Inhibitors
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Aniline Compounds
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Xanthenes
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Cyclin D1
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Fluo-3
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Nitric Oxide
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Nitric Oxide Synthase Type III
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Proto-Oncogene Proteins c-akt
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Thiourea
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Calcium