Involvement of androgen receptor in nitric oxide production induced by icariin in human umbilical vein endothelial cells

被引：42

作者：

Koizumi, Hideki ^{[2
]}

Yu, Jing

Hashimoto, Ryo ^{[2
]}

Ouchi, Yasuyoshi ^{[2
]}

Okabe, Tetsuro ^{[1
]}

机构：

[1] Univ Tokyo, Grad Sch Med, Dept Integrated Tradit Med, Bunkyo Ku, Tokyo 1130033, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Geriatr Med, Tokyo 1130033, Japan

来源：

FEBS LETTERS | 2010年 / 584卷 / 11期

关键词：

Icariin; Endothelial cells; Nitric oxide; Endothelial nitric oxide synthase; Androgen receptor; SYNTHASE; PHOSPHODIESTERASE-5; PATHWAYS;

D O I：

10.1016/j.febslet.2010.04.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Icariin, a flavonoid isolated from Epimedii herba, stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) at Ser1177, Akt (Ser473) and ERK1/2 (Thr202/Tyr204). The icariin-induced eNOS phosphorylation was abolished by an androgen receptor (AR) antagonist, nilutamide in human umbilical vein endothelial cells (HUVECs). Furthermore, it was also reduced in the cells transfected with small interfering RNA in which the expression of AR was broken down. The icariin-induced eNOS phosphorylation was inhibited by wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor and partially attenuated by PD98059, an upstream inhibitor for ERK1/2. These data suggest that icariin stimulates release of NO by AR-dependent activation of eNOS in HUVECs. PI3K/Akt and MAPK-ERK kinase (MEK)/ERK1/2 pathways were involved in the phosphorylation of eNOS by icariin. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：2440 / 2444

页数：5

共 19 条

[1] Icariin stimulates angiogenesis by activating the MEK/ERK- and PI3K/Akt/eNOS-dependent signal pathways in human endothelial cells [J].

Chung, Byung-Hee ;

Kim, Jong-Dai ;

Kim, Chun-Ki ;

Kim, Jung Huan ;

Won, Moo-Ho ;

Lee, Han-Soo ;

Dong, Mi-Sook ;

Ha, Kwon-Soo ;

Kwon, Young-Geun ;

Kim, Young-Myeong .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 376 (02) :404-408

[2] Potent inhibition of human phosphodiesterase-5 by icariin derivatives [J].

Dell'Agli, Mario ;

Galli, Gerrnana V. ;

Del Cero, Esther ;

Belluti, Federica ;

Matera, Riccardo ;

Zironi, Elisa ;

Pagliuca, Giampiero ;

Bosisio, Enrica .

JOURNAL OF NATURAL PRODUCTS, 2008, 71 (09) :1513-1517

[3] VEGF regulation of endothelial nitric oxide synthase in glomerular endothelial cells [J].

Feliers, D ;

Chen, XY ;

Akis, N ;

Choudhury, GG ;

Madaio, M ;

Kasinath, BS .

KIDNEY INTERNATIONAL, 2005, 68 (04) :1648-1659

[4] Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase [J].

Fleming, I ;

Busse, R .

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2003, 284 (01) :R1-R12

[5] Small interfering RNA-mediated down-regulation of caveolin-1 differentially modulates signaling pathways in endothelial cells [J].

Gonzalez, E ;

Nagiel, A ;

Lin, AJ ;

Golan, DE ;

Michel, T .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (39) :40659-40669

[6]

[郭宝林 Guo Baolin], 2003, [中国中药杂志, China Journal of Chinese Materia Medica], V28, P303

[7] Therapeutic potential of nitric oxide donors in the prevention and treatment of atherosclerosis [J].

Herman, AG ;

Moncada, S .

EUROPEAN HEART JOURNAL, 2005, 26 (19) :1945-1955

[8] THE NUCLEAR RECEPTOR SUPERFAMILY - THE 2ND DECADE [J].

MANGELSDORF, DJ ;

THUMMEL, C ;

BEATO, M ;

HERRLICH, P ;

SCHUTZ, G ;

UMESONO, K ;

BLUMBERG, B ;

KASTNER, P ;

MARK, M ;

CHAMBON, P ;

EVANS, RM .

CELL, 1995, 83 (06) :835-839

[9]

Nakatsubo N, 1998, BIOL PHARM BULL, V21, P1247

[10] Effects of icariin on phosphodiesterase-5 activity in vitro and cyclic guanosine monophosphate level in cavernous smooth muscle cells [J].

Ning, Hongxiu ;

Xin, Zhong-Cheng ;

Lin, Guiting ;

Banie, Lia ;

Lue, Tom F. ;

Lin, Ching-Shwun .

UROLOGY, 2006, 68 (06) :1350-1354

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