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|本期目录/Table of Contents|

雌激素膜快速效应对兔血管平滑肌细胞iNOS快速激活的影响

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2015年第6期
页码:
629-633
栏目:
基础研究
出版日期:
2015-07-15

文章信息/Info

Title:
Membrane estrogen receptor mediates the rapid activation of iNOS by estrogen in rabbit vascular smooth muscle cells
作者:
刘海梅1; 徐进文1; 许 研2; 赵晓峰3; 王庭槐3
(1.广州中医药大学生理学教研室，广东 广州 510006；
2.广州市第11人民医院心内科，广东 广州 510530；
3.中山大学中山医学院生理学教研室，广东 广州 510080)
Author(s):
LIU Hai-mei1;  XU Jin-wen1;  XU Yan2;  ZHAO Xiao-feng3;  WANG Ting-huai1
(1.Department of Physiology, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, China；
2.Guangzhou Eleventh People’s, Guangzhou 510530, Guangdong, China；
3.Department of Physiology, Zhongshan Medical College, Sun Yat-sen University, Guangzhou 510080, Guangdong, China)
关键词:
17β-雌二醇; 血管平滑肌细胞; 一氧化氮合酶; 细胞外信号调节激酶; 兔
Keywords:
estrogen;  vascular smooth muscle cell;  nitric oxide synthase;  mitogen-activated protein kinase;  rabbit
分类号:
R977.12
DOI:
-
文献标识码:
A
摘要:
目的 探讨17β-雌二醇（17β-estradiol，E2）通过快速激活诱导型一氧化氮合成酶（iNOS）的活性，调节细胞外信号调节激酶（mitogen-activated protein kinase,p42/44 MAPK）表达抑制血管平滑肌细胞（vascular smooth muscle cells，VSMCs）增殖的机制。方法 在培养的VSMCs的基础上，采用放射免疫测定法(RIA)和Western blot检测E2预处理前后胎牛血清（fetal calf serum，FCS）对VSMCs中诱导型iNOS的活性及磷酸化p42/44 MAPK蛋白和p42/44 MAPK总蛋白表达的影响。采用比色法检测E2预处理后VSMCs中NO含量的变化。结果 E2预处理5 min，即可逆转FCS诱导的iNOS活性下降，此效应在E2预处理15 min时达到高峰，处理30 min后此效应减弱。基因转录抑制剂放线菌素D（actinomycin D，Act D）预处理后对此过程无影响，而三苯氧胺预处理可明显逆转E2诱导的iNOS活性增加。比色法检测上清液中NO的含量显示，E2预处理15 min，NO的含量明显增加。Western blot的结果显示，E2预处理15 min，可明显抑制磷酸化p42/44 MAPK蛋白的表达，而对总p42/44 MAPK蛋白的表达无影响。NO合酶(NOS)抑制剂L-硝基左旋精氨酸甲酯(L-NAME)预处理，可逆转E2诱导的磷酸化p42/44 MAPK的表达下降。结论 E2可通过快速激活iNOS增加NO释放，下调磷酸化p42/44 MAPK的活性，抑制VSMCs增殖。
Abstract:
AIM To investigate the non-genomic effect on inhibition of the proliferation of vascular smooth cells (VSMCs) via activation of iNOS and mitogen-activated protein kinase (p42/44MAPK) by 17β-estradiol. METHODSiNOS activation was determined by radioimmunoassay. Expressions of iNOS, p42/44 MAPK and p42/44 MAPK phosphorylation were measured by Western blot and expression of NO content was detected by colorimetric method. RESULTS In cultured VSMCs, activation of iNOS began to increase after pretreatment with estrogen for 5 min, and the maximum effect took place at 15 min and rapidly reverted thereafter. The effect of E2 on iNOS activation was not affected by actinomycin D but was obviously inhibited by tamoxifen. At the same time, NO production increased significantly after treatment with 17β-estradiol within 15 min. Compared with fetal calf serum, E2 pretreatment of VSMCs for 15 min decreased p42/44MAPK activity and this effect was blocked by L-NAME. CONCLUSION 17β-estradiol rapidly upregulates iNOS activation and NO production and downregulates p42/44 MAPK activation to inhibit VSMC proliferation through a non-genomic effect.

参考文献/References

[1]Wang H,Liu Y,Zhu L,et al.17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway[J].Int J Mol Med,2014,33(3):550-558.
[2]Li F,Yu X,Szynkarski CK,et al.Activation of GPER Induces Differentiation and Inhibition of Coronary Artery Smooth Muscle Cell Proliferation[J]. PLoS One,2013,8(6):e64771.
[3]Ueda K,Lu Q,Baur W,et al.Rapid estrogen receptor signaling mediates estrogen-induced inhibition of vascular smooth muscle cell proliferation[J].Arterioscler Thromb Vasc Biol,2013,33(8):1837-1843.
[4]Liu HM,Zhao XF,Guo LN,et al.Effects of caveolin-1 on the 17beta-estradiol-mediated inhibition of VSMC proliferation induced by vascular injury[J].Life Sci,2007,80(8):800-812.
[5]Cossette ?,Cloutier I,Tardif K,et al.Estradiol inhibits vascular endothelial cells pro-inflammatory activation induced by C-reactive protein[J].Mol Cell Biochem,2013,373(1-2):137-147.
[6]Fu XD,Cui YH,Lin GP,et al.Non-genomic effects of 17beta-estradiol in activation of the ERK1/ERK2 pathway induces cell proliferation through upregulation of cyclin D1 expression in bovine artery endothelial cellsCossette[J].Gynecol Endocrinol,2007,23(3):131-137.
[7]Resanovic I,Rizzo M,Zafirovic S,et al.Anti-atherogenic effects of 17β-estradiol[J].Horm Metab Res,2013,45(10):701-708.
[8]Simoncini T,Hafezi-Moghadam A,Brazil DP,et al.Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase[J].Nature,2000,407(6803):538-541.
[9]Teoh H,Quan A,Leung SW,et al.Differential effects of 17beta-estradiol and testosterone on the contractile responses of porcine coronary arteries[J].Br J Pharmacol,2000,129(7):1301-1308.
[10]Zhang X,Deng H,Wang ZY.Estrogen activation of the mitogen-activated protein kinase is mediated by ER-α36 in ER-positive breast cancer cells[J].J Steroid Biochem Mol Biol,2014,143:434-443.

备注/Memo

备注/Memo:
收稿日期：2014-11-02.
基金项目：国家自然科学基金项目资助（30440028，81202186）
通讯作者：王庭槐，教授，主要从事雌激素心血管疾病防治的机制研究 Email:wangth@mail.sysu.edu.cn
作者简介：刘海梅，副教授，博士 Email:lhmei99@163.com
更新日期/Last Update: 2015-07-23