期刊文献+

硒对大鼠肝细胞凋亡和原癌基因c-myc、c-fos和c-jun表达的影响 被引量:4

Effects of selenium on rat hepatocellular apoptosis,proto-oncogene c-myc, c-fos and c-jun expression
下载PDF
导出
摘要 目的 研究亚硒酸钠对大鼠肝细胞凋亡和原癌基因c myc、c fos和c jun表达的影响。方法 选用大鼠 ,每组 5只 ,用 5、10和 2 0 μmol/kg亚硒酸钠腹腔注射染毒。用末端标记法 (TUNEL)、流式细胞术检测细胞凋亡 ,用Northern斑点杂交方法研究原癌基因c myc、c fos和c jun的表达。结果  5、10和 2 0 μmol/kg的亚硒酸钠染毒大鼠 ,不仅能诱导大鼠肝细胞凋亡 ,细胞凋亡率均较对照组 ( 2 2 2± 0 43 ) %显著增高 ,分别为 ( 3 72± 1 76) % (P <0 0 5 )、( 5 82± 1 42 ) % (P <0 0 1)和 ( 11 76± 1 87) % (P <0 0 1) ,而且还存在着明显的剂量 反应关系。 5、10和 2 0 μmol/kg的亚硒酸钠也能引起大鼠肝细胞c myc、c fos和c junmRNA明显增多 ,免疫组化分析可以检测到表达产物c Myc ,c Fos和c Jun蛋白 ,说明这 3种原癌基因表达增强。结论 一定剂量的亚硒酸钠可以诱导大鼠肝细胞凋亡和原癌基因c myc、c fos和c Objective This study was conducted to explore effects of selenium on rat hepatocellular apoptosis,proto-oncogene c-myc,c-fos and c-jun expression in vivo.Methods Sodium selenite at the doses of 5,10 and 20 μmol/kg were given to rats by i.p.and there were 5 male SD rats in each group. Hepatocellular apoptosis was measured with TdT-mediated dUTP nick end labelling(TUNEL) and flow cytometry. Proto-oncogene c-myc, c-fos and c-jun expression in rat hepatocytes were measured with northern dot hybridization.Results The results showed that sodium selenite at the doses of 5, 10 and 20 μmol/kg, not only induced hepatocellular apoptosis, apoptosis rates were(3.72±1.76)%(P<0.05), (5.82±1.42)%(P<0.01)and(11.76±1.87)%(P<0.01) respectively, but also displayed obvious dose-response relationship. In addition, sodium selenite at these doses resulted in proto-oncogene c-myc, c-fos and c-jun expression significantly, c-Myc,c-Fos and c-Jun protein can be detected in rat hepatocytes with immunohistochemistry.Conclusion selenium at certain doses can induce rat hepatocellular apoptosis,proto-oncogene c-myc, c-fos and c-jun expression significantly in vivo.
出处 《卫生毒理学杂志》 CAS CSCD 北大核心 2004年第2期68-70,共3页 Journal of Health Toxicology
基金 国家自然科学基金资助 (30 2 71 1 1 0 )
关键词 大鼠 肝细胞 细胞凋亡 原癌基因 c-myc C-FOS C-JUN 基因表达 Selenium Apoptosis c-myc c-jun c-fos Proto-oncogene
  • 相关文献

参考文献14

  • 1Cheng WH, Zheng X, Quimby FR,et al. Low levels of glutathione peroxidase 1 activity in selenium-deficient mouse liver affect c-Jun N-terminal kinase activation and p53 phosphorylation on Ser-15 in pro-oxidant-induced aponecrosis. Biochem J,2003,370: 927-9
  • 2Rao L, Puschner B, Prolla TA. Gene expression profiling of low selenium status in the mouse intestine:transcriptional activation of genes linked to DNA damage, cell cycle control and oxidative stress. J Nutr ,2001,131: 3175-3181.
  • 3Lu J, Kaeck M,Jiang C, et al. Selenite induction of DNA strand breaks and apoptosis in mouse leukemic L1210 cells. Biochem Pharmacol, 1994, 47: 1531-1535.
  • 4Stewart MS, Spallholz JE, Neldner KH, et al. Selenium compounds have disparate abilities to impose oxidative stress and induce apoptosis. Free Radio Biol Med, 1999, 26:42-48.
  • 5Zhong W, Oberley TD. Redox-mediated effects of selenium on apoptosis and cell cycle in the LNCaP human prostate cancer cell line. Cancer Res, 2001 , 61:7071-7078.
  • 6Yang CF, Shen HM, Ong CN. Ebselen induces apoptosis in HepG2 cells through rapid depletion of intracellular thiols.Arch Biochem Biophys, 2000, 374:42-52.
  • 7Shen HM, Yang CF, Ding WX, et al. Superoxide radical-initiated apoptotic signalling pathway in selenite-treated HepG(2)cells: mitochondria serve as the main target. Free Radic Biol Med, 2001, 30:9-21.
  • 8Juin P, Hunt A, Littlewood T, et al. c-Myc functionally cooperates with Bax to induce apoptosis. Mol Cell Biol, 2002, 22:6158-6169.
  • 9Taimor G, Rakow A, Piper HM. Transcription activator protein 1 (AP-1) mediates NO-induced apoptosis of adult cardiomyocytes. FASEB J, 2001, 15:2518-2520.
  • 10Vafa O, Wade M, Kern S, et al. c-Myc can induce DNA damage, increase reactive oxygen species, and mitigate p53function: a mechanism for oncogene-induced genetic instability. Mol Cell, 2002,9:1031-1044.

二级参考文献5

共引文献14

同被引文献48

引证文献4

二级引证文献14

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