• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Involvement of protein kinase C in crystalline silica-induced activation of the MAP kinase and AP-1 pathway.
【24h】

Involvement of protein kinase C in crystalline silica-induced activation of the MAP kinase and AP-1 pathway.

机译：蛋白激酶C参与结晶二氧化硅诱导的MAP激酶和AP-1途径的激活。

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

Crystalline silica has long been well established as a fibrogenic agent, and recent evidence has implicated it as a potential human carcinogen. However, the mechanisms of silica-induced disease development and progression are not well understood. Our previous studies demonstrated that crystalline silica is able to activate activator protein-1 (AP-1) through mitogen-activated protein kinase (MAPK) pathways. The present study investigates the possible involvement of protein kinase C (PKC) in silica-induced activation of the MAPK/AP-1 signal transduction pathway. Treatment of mouse epidermal cells (JB6 cell line) with freshly fractured silica stimulated translocation of PKCalpha and PKCepsilon from the cytosol to the membrane and activated AP-1 transcription activity. Pretreatment of cells with PKC inhibitors, including RO-32-0432, calphostin C, and bisindolylmaleimide I, inhibited silica-induced AP-1 activation and phosphorylation of ERKs and p38 kinase. These inhibitory effects by PKC inhibitors were dose dependent. Furthermore, overexpression of dominant negative mutant (DNM) of PKCalpha or PKCepsilon markedly blocked AP-1 activation as well as phosphorylation of ERKs and p38 kinase induced by freshly fractured silica. These results demonstrate that PKCalpha and PKCepsilon are essential in silica-induced AP-1 activation through the MAP kinase (ERKs and p38 kinases) pathway.
机译：长期以来，结晶二氧化硅已被广泛确立为一种成纤维剂，最近的证据表明它是潜在的人类致癌物。然而，二氧化硅诱导的疾病发展和进展的机制尚不清楚。我们以前的研究表明，结晶二氧化硅能够通过有丝分裂原激活的蛋白激酶（MAPK）途径激活激活蛋白1（AP-1）。本研究调查了蛋白激酶C（PKC）可能参与了二氧化硅诱导的MAPK / AP-1信号转导途径的激活。用新鲜破碎的二氧化硅处理小鼠表皮细胞（JB6细胞系）可刺激PKCalpha和PKCepsilon从胞浆转移至膜并激活AP-1转录活性。用PKC抑制剂（包括RO-32-0432，钙磷蛋白C和双吲哚基马来酰亚胺I）预处理细胞可抑制二氧化硅诱导的AP-1活化以及ERK和p38激酶的磷酸化。 PKC抑制剂的这些抑制作用是剂量依赖性的。此外，PKCalpha或PKCepsilon的显性负突变体（DNM）的过表达显着阻断了AP-1的活化以及新近断裂的二氧化硅诱导的ERK和p38激酶的磷酸化。这些结果表明，PKCalpha和PKCepsilon在通过MAP激酶（ERK和p38激酶）途径诱导二氧化硅诱导的AP-1激活中是必不可少的。

著录项

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