尼克酰胺腺嘌呤二核苷酸磷酸氧化酶介导血管紧张素II诱导的肾小球系膜细胞增殖
DOI:
作者:
作者单位:

作者简介:

通讯作者:

中图分类号:

基金项目:

江苏省自然科学基金(BK2007259);江苏省"科教兴卫"工程医学重点人才基金(RC2007015)


Nicotinamide adenine dinucleotide phosphate oxidase-derived reactive oxygen species mediated angiotensin Ⅱ-induced human mesangial cell proliferation
Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
  • |
  • 文章评论
    摘要:

    目的:探讨活性氧(ROS)在血管紧张素Ⅱ(AngⅡ)诱导的c-Jun氨基末端激酶(JNK)/活化蛋白(AP-1)信号通路活化及系膜细胞增殖中的作用并探讨其来源-方法:体外培养人肾小球系膜细胞,应用3H-胸腺嘧啶(3H-TdR)掺入法和细胞计数测定系膜细胞增殖;荧光探针2,7-二氯二氢荧光素乙酰乙酸(DCFDA)检测细胞内ROS 的产生;化学发光法检测尼克酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶活性;Western Blot 检测JNK活化-结果:AngⅡ呈时间依赖性和剂量依赖性促进肾小球系膜细胞ROS产生-AngⅡ刺激3 min,系膜细胞内ROS 产生明显增加,至60 min达到高峰-AT1R血管紧张素Ⅱ-1型受体(AT1R)拮抗剂氯沙坦完全阻断了AngⅡ诱导的ROS 产生-NADPH 氧化酶抑制剂夹竹桃麻素和二联苯碘(DPI)几乎完全阻断AngⅡ诱导的ROS 产生,而线粒体复合体Ⅰ抑制剂鱼藤酮-黄嘌呤氧化酶抑制剂别嘌醇-环氧化酶抑制剂吲哚美辛-脂氧化酶抑制剂去甲二氢化愈创木酸-细胞色素P450 氧化酶抑制剂酮康唑以及一氧化氮合成酶抑制剂N-硝基-L-精氨酸甲酯(L-NAME)对AngⅡ诱导的ROS 产生均无明显影响-AngⅡ显著刺激NADPH氧化酶活化及p47phox和p67phox膜转位-氯沙坦-乙酰半胱氨酸(NAC)-夹竹桃麻素和DPI 阻断AngⅡ诱导的JNK/AP-1活化和系膜细胞增殖-结论:NADPH 氧化酶来源的ROS调控AngⅡ诱导的JNK/AP-1信号通路活化及系膜细胞增殖-NADPH氧化酶抑制剂能显著抑制AngⅡ诱导的系膜细胞增殖,可能具有一定的治疗作用-

    Abstract:

    Objective:The purpose of this study was to detect the signaling pathways involved in angiotensinⅡ(AngⅡ)-induced mesangial cell(MC) proliferation. Methods:The incorporation of 3H-thymidine(3H-TdR) and cell count were used as the measure of mesangial cell proliferation. Reactive oxygen species(ROS) production was determined by DCFDA fluorescence. Nicotinamide adenine dinucleotide phosphate(NADPH) oxidase activity was examined by lucigenin chemiluminescence. c-Jun animoterminal kinase(JNK) activation was assayed by Western blot. Results:AngⅡ time-dependently and dose-dependently increased intracellular ROS production in cultured human MCs as early as 3 min and peak at 60 min. Incubation with different dose of AngⅡ(1 nmol/L,10 nmol/L, and 100 nmol/L AngⅡ) for 60 min, ROS production increased for 1.82-, 2.92-, and 4.08-fold, respectively. AngⅡ-induced ROS generation was inhibited by the AT1R antagonist losartan but not the AT2R antagonist PD123319, as well as NADPH oxidase inhibitors diphenyleneiodonium sulfate(DPI) and apocynin. In contrast, inhibitors of other oxidant-producing enzymes, including rotenone, allopurinol, indomethacin, nordihydroguiaretic acid, ketoconazole and G-nitro-L-arginine methyl ester(L-NAME) have no effect on AngⅡ-induced ROS production and MC proliferation. AngⅡ treatment induced translocation of cytosolic of p47phox and p67phox to the membrane and p47phox and p67phox gene expression. Conclusion:NADPH oxidase-derived ROS involved in AngⅡ-induced JNK/AP-1 activation and mesangial cell proliferation.

    参考文献
    相似文献
    引证文献
引用本文

吴红梅,张爱华,黄松明,丁桂霞,张维真,鲍华英,陈荣华.尼克酰胺腺嘌呤二核苷酸磷酸氧化酶介导血管紧张素II诱导的肾小球系膜细胞增殖[J].南京医科大学学报(自然科学版),2008,28(12):1541-1546

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
  • HTML阅读次数:
  • 引用次数:
历史
  • 收稿日期:2008-09-05
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期:
  • 出版日期: