The mechanism of (R,R) ZX-5 on increasing NO release.
(R,R) ZX-5 has been proven to have positive effects on choroidal blood flow without affecting the sclera and ciliary bodies in New Zealand white rabbits. This study was designed to investigate the mechanisms of (R,R) ZX-5 on improving the choroidal blood flow and promoting NO production. HUVECs (human umbilical vein endothelial cells) were used to determine the production of eNOS, p-eNOS, AKT and Erk1/2 by Western blot analysis. iNOS and eNOS mRNA levels were investigated by RT-PCR and the effect of (R,R) ZX-5 on NO production were determined by eNOS activity assay. We found (R,R) ZX-5 upregulated protein expression of eNOS and iNOS, increased NO production, and reduced ERK and Akt protein level. Therefore, (R,R) ZX-5 may promote the choroidal blood flow in New Zealand white rabbits without affecting the blood flow in the iris or ciliary bodies via increasing NO production. These results suggest that (R,R) ZX-5 may function to cure and prevent Age-related macular degeneration (AMD).
Department of Marine Pharmacy, College of Life Science and Technology, China Pharmaceutical University, Nanjing 210009, Jiangsu Province, China; E-Mails: xuhanmei@yahoo.com.cn (H.-M.X.); tiandezhijian@126.com (J.W.); panli0225@163.com (L.P.); hongyin7719@sina.com (H.L.); wwq1979@163.com (W.W.).
Han-Mei
HM
Xu
Jin
J
Wei
Li
L
Pan
Hongying
H
Lin
Weiqiang
W
Wang
Yihua
Y
Zhang
Zilong
Z
Shen
D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
C480782:1-phenyl-3-(3-methoxy-2-propoxy-5-(4-(3,4,5-trimethoxyphenyl)-1,3-dithiolane-2-yl)phenyl)thiourea; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D013890:Thiourea