• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Translational Stroke Research >Heat Shock Proteins in the Brain: Role of Hsp70, Hsp 27, and HO-1 (Hsp32) and Their Therapeutic Potential
【24h】

Heat Shock Proteins in the Brain: Role of Hsp70, Hsp 27, and HO-1 (Hsp32) and Their Therapeutic Potential

机译：脑中的热休克蛋白：Hsp70，Hsp 27和HO-1（Hsp32）的作用及其治疗潜力

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Heat shock proteins (Hsps) are induced by heat shock via heat shock factor proteins binding to heat shock elements in their promoters. Hsp70 is massively induced in response to misfolded proteins following cerebral ischemia in all cell types but is induced mainly in neurons in the ischemic penumbra. Overexpression of Hsp70 via transgenes and viruses or systemic administration of Hsp70 fusion proteins that allow it to cross the blood brain barrier protects the brain against ischemia in most reported studies. Hsp27 can exist as unphosphorylated large oligomers that prevent misfolded protein aggregates and improve cell survival. P-Hsp27 small oligomers bind specific protein targets to improve survival. In the brain, protein kinase D phosphorylates Hsp27 following ischemia which then binds apoptosis signal-regulating kinase 1 to prevent MKK4/7, c-Jun NH(2)-terminal kinase, and Jun-induced apoptosis, and decrease infarct volumes following focal cerebral ischemia. Heme oxygenase-1 (HO-1) metabolizes heme to carbon monoxide, ferrous ion, and biliverdin. CO activates cGMP to promote vasodilation, and biliverdin is converted to bilirubin which can serve as an anti-oxidant, both of which may contribute to the reported protective role of HO-1 in cerebral ischemia and subarachnoid hemorrhage. However, ferrous ion can react with hydrogen peroxide to produce pro-oxidant hydroxyl radicals which may explain the harmful role of HO-1 in intracerebral hemorrhage. Heat shock proteins as a class have great potential as treatments for cerebrovascular disease and have yet to be tested in the clinic.
机译：热激蛋白（Hsps）是通过热激因子蛋白结合到其启动子中的热激元件而被热激诱导的。在所有细胞类型的脑缺血后，对Hsp70的错误折叠蛋白均会大量诱导，但主要在缺血半影的神经元中诱导。在大多数报道的研究中，通过转基因和病毒使Hsp70过度表达，或全身性给予Hsp70融合蛋白使其穿过血脑屏障，可以保护脑部免受缺血。 Hsp27可以以未磷酸化的大寡聚体形式存在，可防止错误折叠的蛋白质聚集体并提高细胞存活率。 P-Hsp27小寡聚物结合特定的蛋白质靶标，以提高生存率。在大脑中，蛋白激酶D在缺血后使Hsp27磷酸化，然后与凋亡信号调节激酶1结合，以阻止MKK4 / 7，c-Jun NH（2）末端激酶和Jun诱导的凋亡，并减少局灶性脑梗死后的梗死体积缺血。血红素加氧酶-1（HO-1）将血红素代谢为一氧化碳，亚铁离子和胆绿素。 CO激活cGMP促进血管舒张，而biliverdin转化为胆红素，可作为抗氧化剂，两者均可能有助于报告HO-1在脑缺血和蛛网膜下腔出血中的保护作用。然而，亚铁离子可与过氧化氢反应生成促氧化剂羟基，这可解释HO-1在脑出血中的有害作用。一类热休克蛋白具有治疗脑血管疾病的巨大潜力，尚未在临床上进行测试。

著录项

  • 来源
    《Translational Stroke Research》 |2013年第6期|685-692|共8页
  • 作者

    Frank R Sharp; Xinhua Zhan; Da-Zhi Liu;

  • 作者单位

    Department of Neurology University of California at Davis">(1);

    MIND Wet Labs MIND Institute University of California Medical Center University of California at Davis">(2);

    Department of Neurology University of California at Davis">(1);

    MIND Wet Labs MIND Institute University of California Medical Center University of California at Davis">(2);

    Department of Neurology University of California at Davis">(1);

    MIND Wet Labs MIND Institute University of California Medical Center University of California at Davis">(2);

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Brain ischemia; Hemorrhage; Heat shock proteins; Immune; Apoptosis; Heme;

    机译：脑缺血;出血;热激蛋白;免疫细胞凋亡;血红素;

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号