期刊文献+

金雀异黄素抑制缺氧人视网膜色素上皮细胞VEGF表达机制的初步研究

Inhibitory effects of genistein on hypoxia-induced VEGF expression in ARPE-19 cells
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摘要 目的:进一步明确金雀异黄素(Gen)抑制缺氧人视网膜色素上皮细胞(RPE)血管内皮生长因子(VEGF)表达的机制。方法:以体外正常情况为对照,建立人RPE缺氧模型并经不同浓度Gen干预后,通过RT-PCR检测VEGF及其转录调节因子c-fos、c-jun、缺氧诱导因子(HIF)-1α、HIF-2α、HIF-3αmRNA的表达水平,了解Gen是否通过对VEGF的转录因子活性调节而影响VEGF的表达。结果:缺氧能使人RPE细胞的VEGF、c-fos、c-jun及HIF-2α、HIF-3αmRNA水平增高,对HIF-1α无影响;Gen能抑制缺氧诱导的VEGF表达;在所检测的VEGF转录因子中,Gen只对HIF-2α的转录有抑制作用。结论:Gen抑制VEGF表达的作用部分是通过抑制其转录调节因子HIF-2α转录实现的。 Objective: To study the regulatory mechanism of genistein(Gen) in inhibiting hypoxia-induced vascular endothelial growth factor (VEGF) expression in ARPE-19 cells. Methods: Pretreated with different concentrations of Gen, ARPE-19 cells were exposed to hypoxia or normoxia conditions for 24 h ,then the expression of VEGF and c-fos,c-jun,HIF-1α,HIF-2α,HIF- 3αmRNA was detected by RT-PCR. Results: The expression of VEGF,c-fos,c-jun,HIF-2α,HIF-3α mRNA level was increased under hypoxia condition but HIF-1α expression was not changed; Gen could decrease the expression of hypoxia-induced VEGF. HIF-2α was the only factor inhibited by Gen in all the transcription factor we observed. Conclusion:The Inhibitory effects of Gen on hypoxia-induced VEGF expression in ARPE-19 cells may be partly mediated by HIF-2α at the transcriptional level.
出处 《南京医科大学学报(自然科学版)》 CAS CSCD 北大核心 2006年第5期305-309,共5页 Journal of Nanjing Medical University(Natural Sciences)
基金 南京医科大学创新基金资助项目(CX2001003)
关键词 金雀异黄素 ARPE-19 缺氧 血管内皮生长因子 AP-1 缺氧诱导因子 genistein ARPE-19 hypoxia vascular endothelial growth factor AP-1 HIF
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参考文献15

  • 1邹颖,王斌,肖继皋,袁志兰.金雀异黄素对氯化钴诱导的兔视网膜色素上皮细胞血管内皮生长因子表达的影响[J].南京医科大学学报(自然科学版),2003,23(2):142-145. 被引量:10
  • 2周青,袁志兰,戈应滨,王斌.金雀异黄素对缺氧诱导的人ARPE-19细胞VEGF表达的抑制作用[J].南京医科大学学报(自然科学版),2005,25(8):576-579. 被引量:4
  • 3Brown LF, Detmar M, Clafley K, et al. Vascular permeability factor/vascular endothelial growth factor:a muhifunctional angiogenic cytokine [J ]. EXS,1997,79: 233-269. 被引量:1
  • 4Sandstrom M ,Johansson M ,Sandstrom J,et al. Expression of the proteolytic factor,t-PA and uPA,PAI-1 and VEGF during malignant glioma progression [J]. Int J Dev Neurosci, 1999, 17(5-6) :473-481. 被引量:1
  • 5Li Y, Sarkar FH. Gene expression profiles of genisteintreated PC3 prostate cancer cells [J]. J Nutr, 2002,132:3623-3631. 被引量:1
  • 6Su SJ, Yeh TM, Chuang WJ, et al. The novel targets for anti-angiogenesis of genistein on human cancer cells [J].Biochem Pharmacol, 2005,69(2) :307-318. 被引量:1
  • 7Covello KL,Simon MC. HIFs, hypoxia, and vascular development[J]. Curt Top Dev Biol,2004,62:37-54. 被引量:1
  • 8Semenza GL, Wang GL. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation [J ]. Mol Cell Biol, 1992,12 : 5447-5454. 被引量:1
  • 9Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF [J]. Science, 2001,294: 1337. 被引量:1
  • 10Tian H, McKnight SL, Russell DW. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells[J]. Genes & Dev,1997,11:72-82. 被引量:1

二级参考文献23

  • 1单俊杰,袁志兰,李华,王斌.金雀异黄素对缺氧诱导的人ARPE-19细胞内碱性成纤维细胞生长因子蛋白表达的影响[J].国际眼科杂志,2004,4(3):413-416. 被引量:7
  • 2李华,严虹,潘金顺,王斌.金雀异黄素抑制氯化钴诱导的人视网膜色素上皮细胞缺氧诱导因子1α表达的研究[J].医学研究生学报,2004,17(11):973-975. 被引量:5
  • 3Blancher C, Moore JW, Roberteson N, et al. Effects of ras and von Hippel-Lindau (VHL) gene mutations on hypoxia-inducible factor (HIF)-lalpha, HIF-2alpha,and vascular endothelial growth factor expression and their regulation by the phosphatidylinositol 3'-kinase/Akt signaling pathway [J]. Cancer Research,2001,61 (19):7349-7355. 被引量:1
  • 4Berra E, Pages G, Pouyssegur J. MAP kinases and hypoxia in the control of VEGF expression[J]. Cancer &Metastasis Reviews,2000, 19(1-2): 139-145. 被引量:1
  • 5Bertges DJ,Berg S,Fink MP,et al. Regulation ofhypoxiainducible factor 1 in enterocytic cells [J].J Surg Res,2002,106(1 ): 157-165. 被引量:1
  • 6Li Y, Sarkar FH. Down-regulation of invasion and angiogenesis-related genes identified by cDNA microarray analysis of PC3 prostate cancer cells treated with genistein[J]. Cancer Lett, 2002,186 (2): 157-164. 被引量:1
  • 7Sone H,Kawakmi Y, Kuda Y, et al. Vascular endothelial growth factor is induced by long-term high glucose concentration and up-regulated by acute glucose deprivation in cultured bovine retinal pigment epithelial cells [J]. Biochem Biophys Res Comm, 1996,221(1):193-198. 被引量:1
  • 8Miller JW. Vascular endothelial growth factor and ocular neovascularization [J ] .Am J Pathol, 1997,151(1): 13-23. 被引量:1
  • 9Webster KA, Discher DJ, Bishopric NH.Induction and nuclear accumulation of fos and jun proto-oncigenes in hypoxia cardiac myocyts [J].Biol Chem, 1993,268:16852. 被引量:1
  • 10Miller JW. Vascular endothelial growth factor and ocular neovascularization[J]. Am J Pathol, 1997,151(1):13-23. 被引量:1

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