期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

抑制性PAS蛋白抑制血管内皮生长因子的表达 被引量：1

Inhibitory effect of inhibitory PAS domain protein on expression of vascular endothelial growth factor
下载PDF
导出
摘要 目的:探讨抑制性PAS蛋白质(inhibitory PAS do-main protein, IPAS)对缺氧诱导因子1α(hypoxia inducible factor-1α,HIF-1α)的活性和血管内皮生长因子(vascular endothelial growth factor,VEGF)表达的抑制作用。方法:在缺氧条件和正常氧条件,采用脂质体转染法,将pcDNA3-HIF-1α质粒、含促红细胞生成素(erythropoietin,EPO)增强子的荧虫素酶(lu-ciferase)报告基因和不同量的pcDNA3-IPAS质粒共转染NIH 3T3细胞,通过检测荧虫素酶的活性以反映HIF-1α的活性;以转染pcDNA3-IPAS为IPAS组,转染pcDNA3为对照组,采用半定量RT-PCR法,检测转染两组NIH-3T3细胞中VEGF mRNA的表达。结果:转染pcDNA3-IPAS的NIH 3T3细胞的荧虫素酶活性较对照组明显降低,且随转染量的增加荧虫素酶的活性降低越明显;转染pcDNA3-IPAS的NIH 3T3细胞的VEGF mRNA表达较对照组明显降低。结论:IPAS通过降低HIF-1α的活性抑制了VEGF mRNA的表达。 AIM: To study the inhibitory effect of inhibitory PAS domain protein (IPAS) on the activity of hypoxia inducible factor-1 α(HIF-1α) and the expression of vascular endothelial growth factor (VEGF).· METHODS: Luciferase reporter plasmids containing the EPO enhancers were co-transfected with pcDNA3-HIF-1α and pcDNA3-IPAS in NIH 3T3 fibroblast cells subjected to normoxia or 16h of hypoxia. The activity of HIF-1αwas identified by measuring the relative enzymatic activity of luciferase. MRNAs were isolated from pcDNA3-HIF-1α and pcDNA3 or pcDNA3-IPAS co-transfected cells, and analysed by semi-quantitative RT-PCR.· RESULTS: The activity of luciferase of NIH-3T3 transfected pcDNA3-IPAS was much lower than that in the control group, and the higher dose of pcDNA3-IPAS, the lower activity of luciferase. The expression of the mRNA of VEGF of NIH-3T3 transfected pcDNA3-IPAS was decreased compared with the cells transfected pcDNA3.· CONCLUSION: IPAS inhibits the expression of mRNA of VEGF by reducing the activity of HIF-1α.·
作者 许惠卓 夏晓波 刘双珍 李岩
机构地区 中国长沙中南大学湘雅医院眼科 美国Texas大学MDAnderson癌症中心
出处 《国际眼科杂志》 CAS 2004年第1期69-71,共3页 International Eye Science
关键词 抑制性PAS蛋白 血管内皮生长因子 IPAS 基因表达 缺氧诱导因子l HIF-l inhibitory PAS domain protein hypoxia inducible factor-1α vascular endothelial growth factor
分类号 R770.2 [医药卫生—眼科]
  • 相关文献

参考文献6

  • 1Wang GL, Semenza GL. Characterization of hypoxia inducible factor 1 and regulation of DNA binding activity by hypoxia. J Biol Chem, 1993;268:21513-21518
  • 2Makino Y, Cao R, Svensson K. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature, 2001;414(6863):550-554
  • 3Semenza GL. Targeting HIF-1 for cancer therapy. Nat Rev Cancer, 2003;3(10):721-732
  • 4Makino Y, Kanopka A, Wilson WJ. Inhibitory PAS domain protein (IPAS)is a hypoxia-inducible splicing variant of the hypoxia-inducible factor-3alpha locus. J Biol Chem, 2002;277(36):32405-32408
  • 5Miyamoto N, Mandai M, Takagi H. Contrasting effect of estrogen on VEGF induction under different oxygen status and its role in murine ROP. Invest Ophthalmol Vis Sci, 2002 ;43 (6): 2007 -2014
  • 6夏晓波,周霞,蒋幼芹.青光眼基因治疗的研究[J].国际眼科杂志,2003,3(2):52-54. 被引量：1

二级参考文献13

  • 1Loewen N, Babler C ,Tco WL, et al. Preservation of aqueous outflow facility after second-generation F1V vector-mediated expression of maker genes in anterior segments of human eyes. Invest Ophthalmol Vis Sci, 2002;43( 12): 3686-3690.
  • 2Kaufman PL, Jia WW, Tan J, et al. A perspective of gene therapy in the glaucomas. Surv Ophthalmol, 1999;43(1):91-97.
  • 3Borras T,Brandt CR,Nickells R,et al. Gene therapy for glaucoma:Treating a multifaceted chronic disease. Invest Ophthalmol Vis Sci, 2002;43(8):2513-2518.
  • 4Angella GJ, Sherwood MB, Balasubramanian L, et al. Enhanced short-term plasmid transfection of filtration surgery tissues. Invest Ophthalmol Vis Sci,2000;41(13):4158-4162.
  • 5Kee CW,Sobn SS,Hwang JM. Stromelysin gene transfer into human cultured trabecular cells and rat trabecular meshwork in vivo. Invest Ophthalmol Vis Sci, 2002;42(12):2856-2860.
  • 6Sakamoto T, Oshima Y, Nakagawa K, et al. Target gene transfer of tissue plasminogen activator to cornea by electric pulse inhibits intracameral fibrin formation and corneal cloudiness. Hum Gene Ther, 1999; 10(15):2551-2557.
  • 7Perkins TW, Faha B, Ni M, et al. Adenovirus-mediated gene therapy using human p21WAF-1/Cip-1 to prevent wound healing in a rabbit model of glaucoma filtration surgery. Arch Ophthalmol,2002; 120(7):941-949.
  • 8Pines, G, Danbolt, N C, BjΦras M, et al. Cloning and expression of a rat brain L-glutamate transporter. Nature, 1992;360:464-467.
  • 9Damji KF. Advances in molecular genetics of glaucoma: a perspective for the clinician. Semin Ophthalmol,1999;14(3):171-179.
  • 10Bennett J, Maguire AM. Gene therapy for ocular disease. Mol Ther,2000;1 (6):501-505.

同被引文献18

  • 1Mclaren J. Vascular endothelial growth factor and endothelial angiogenesis. Humrepord Update, 2000, 6:45
  • 2Ferrara N. Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Inrern, 1999, 56:794
  • 3Dvorak HF, Brown LF, detmar M et al. Vascular permeability factor(vascular endothelial growth factor ) , microvascular hypenneability,and angiogenesis. Am J Pathol, 1995, 146:1029
  • 4Gleadle JM, Rateliffe PJ. Induction of hypoxia - inducible factor - 1,erythropoietin, vascular endothelial growth factor, and glucose transporter- 1 by hypoxia: Evidence against a regulatory role for Src Kinase.Blood, 1997, 89:503
  • 5Neufeld G, Cohen T, Gengrinovitch S et al. Vascular endothelial growth factor (VEGF) and its receptors. FASEB J, 1999, 13:9
  • 6Smith SK. Angiogenesis. Semin Repord Endocrinol, 1997, 15:221
  • 7Peter B, Monika S, Andreas Oet al. Expression of hypoxia - inducible factor 1 & in epithelial ovarian tumors: its impact on prognosis and on response. Clin Cancer Res, 2001, 7:1661
  • 8Christine CH, Mei L, Gary GC et al. Regulation of hypoxia - inducible factor 1 expression and function by the mammalian target of rapamycin.Mol and Cell Biol, 2002, 22 (20) : 7004
  • 9Pugh CW, Ratcliffe PJ. Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med, 2003, 9:677
  • 10Mazure NM, Brahimi - Horn MC, Pouyssegur J. Protein kinases and the hypoxia - inducible factor 1. two switches in angiogenesis. Curr Pharm Des, 2003, 9:531

引证文献1

国际眼科杂志
2004年 第1期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部