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Molecular Mechanisms of (R,R)ZX-5 on NO Synthesis and Its Anti-Angiogenic Effect

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Author(s): Li Pan | Jia-Liang Hu | Wen-Jing Wang | Xiao-Juan Zhang | Jin Wei | Zhen-Dong Liu | Yi-Hua Zhang | Han-Mei Xu

Journal: International Journal of Molecular Sciences
ISSN 1422-0067

Volume: 13;
Issue: 3;
Start page: 2717;
Date: 2012;
Original page

Keywords: (R | R)ZX-5 | age-related macular degeneration | choroidal neovascularization | signal pathways | angiogenesis

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 Ca2+ 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-Ca2+-eNOS pathways. Additionally, (R,R)ZX-5 can inhibit angiogenesis.
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