Role of inducible nitric oxide synthase in the vascular smooth muscle cells cycle arrest induced by 17β-estradiol
- Author:
- No author available
- Journal Title:
- ACTA PHYSIOLOGICA SINICA
- Issue:
- 6
- DOI:
- 10.3321/j.issn:0371-0874.2003.06.011
- Key Word:
- 血管平滑肌;雌激素;一氧化氮;一氧化氮合酶;细胞周期
Abstract： 利用大鼠血管平滑肌细胞(vascular smooth muscle cells,VSMC)作为模型,观察17β-雌二醇(17β-estradiol,E2)对VSMC诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)活性和蛋白表达的影响,并探讨其在内皮素-1(endothlin 1,ET-1)刺激的VSMC周期循环中的作用.检测指标包括同位素法测定iNOS的活性,免疫印迹法(western blot)检测iNOS蛋白表达,流式细胞仪检测细胞周期,观察一氧化氮合酶(nitric oxide synthase,NOS)抑制剂NG-硝基左旋精氨酸甲酯(NG-nitro-L-arginine methylester,L-NAME)对E2抑制VSMC细胞周期的影响.结果显示,E2明显增加iNOS的活性和蛋白表达,在30 min和12 h时能诱导VSMC的iNOS活性明显增加,而60 min和24 h时VSMC的iNOS活性与对照组无显著差异,不呈明显浓度依赖性,雌激素受体(estrogen receptor,ER)拮抗剂Tamoxifen和L-NAME能明显抑制E2诱导的VSMC iNOS活性增加;E2增加VSMC的iNOS蛋白表达的作用在3 h时起效,12 h达高峰,以后逐渐下降,呈浓度依赖性,Tamoxifen能明显抑制E2诱导的VSMC iNOS蛋白表达;E2明显抑制ET-l诱导的S期细胞百分比和G2+S/G1增加,使VSMC在G1期发生细胞周期阻滞,这些作用可被预先给予L-NAME所明显减轻.上述结果提示,E2使ET-1刺激的VSMC细胞周期循环在G1期发生阻滞与增加VSMC iNOS活性有关,该作用至少部分通过ER介导.
- [1]杨丹,谈智,刘培庆,等.一氧化氮在17-β雌二醇抑制血管平滑肌细胞增殖和原癌基因c -fos表达中的作用[J].2002,(1).
- [2]Valeria, Zancan,Sabrina, Santagati,Chiara, Bolego,etc.17β-Estradiol Decreases Nitric Oxide Synthase II Synthesis in Vascular Smooth Muscle Cells.[J].1999,140(5).
- [3]R, Ross.The pathogenesis of atherosclerosis: a perspective for the 1990s.[J].1993,362(6423).
- [4]H, Ueno,S, Masuda,S, Nishio,etc.Adenovirus-mediated transfer of cyclin-dependent kinase inhibitor-p21 suppresses neointimal formation in the balloon-injured rat carotid arteries in vivo.[J].1997,811.
- [5]Linda Shaw,Michael J Taggart,Clare Austin.Mechanisms of 17 β-oestradiol induced vasodilatation in isolated pressurized rat small arteries[J].2000,129(3).
- [6]Y J, Geng,M, Almqvist,G K, Hansson.cDNA cloning and expression of inducible nitric oxide synthase from rat vascular smooth muscle cells.[J].1994,1218.
- [7]Tzeng E,Kovesdi I,Lizonova A,etc.Nitric oxide prevents p21 degradation with the ubiquitin-proteasome pathway in vascular smooth muscle cells.[J].2000,31(2).
- [8]Yukio Hirata,Yasuyuki Takagi,Shoichiro Takata,etc.Calcitonin gene-related peptide receptor in cultured vascular smooth muscle and endothelial cells[J].1988,151(3).
- [9]Mendelsohn ME,Karas RH.The protective effects of estrogen on the cardiovascular system.[J].1999,340(23).
- [10]Yan Z.-q.,Hansson G. K..Overexpression of Inducible Nitric Oxide Synthase by Neointimal Smooth Muscle Cells[J].1998.
- [11]Yoshiyuki Rikitake,Ken-ichi Hirata,Seinosuke Kawashima,etc.Inhibitory effect of inducible type nitric oxide synthase on oxidative modification of low density lipoprotein by vascular smooth muscle cells[J].1998,136(1).