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Molecular Mechanisms of (R,R)ZX-5 on NO Synthesis and Its Anti-Angiogenic Effect
State Key Laboratory of Natural Medicines, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, China
Department of Pharmacy, University of China Pharmaceutical, Nanjing 210009, China
* Authors to whom correspondence should be addressed.
Received: 24 November 2011; in revised form: 4 February 2012 / Accepted: 14 February 2012 / Published: 29 February 2012
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.
Keywords: (R,R)ZX-5; age-related macular degeneration; choroidal neovascularization; signal pathways; angiogenesis
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Pan, L.; Hu, J.-L.; Wang, W.-J.; Zhang, X.-J.; Wei, J.; Liu, Z.-D.; Zhang, Y.-H.; Xu, H.-M. Molecular Mechanisms of (R,R)ZX-5 on NO Synthesis and Its Anti-Angiogenic Effect. Int. J. Mol. Sci. 2012, 13, 2717-2726.
Pan L, Hu J-L, Wang W-J, Zhang X-J, Wei J, Liu Z-D, Zhang Y-H, Xu H-M. Molecular Mechanisms of (R,R)ZX-5 on NO Synthesis and Its Anti-Angiogenic Effect. International Journal of Molecular Sciences. 2012; 13(3):2717-2726.
Pan, Li; Hu, Jia-Liang; Wang, Wen-Jing; Zhang, Xiao-Juan; Wei, Jin; Liu, Zhen-Dong; Zhang, Yi-Hua; Xu, Han-Mei. 2012. "Molecular Mechanisms of (R,R)ZX-5 on NO Synthesis and Its Anti-Angiogenic Effect." Int. J. Mol. Sci. 13, no. 3: 2717-2726.