• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cellular Signalling >Pertassis toxin promotes macrophage survival through inhibition of acid sphingomyelinase and activation of the phosphoinositide 3-kinase/protein kinase B pathway
【24h】

Pertassis toxin promotes macrophage survival through inhibition of acid sphingomyelinase and activation of the phosphoinositide 3-kinase/protein kinase B pathway

机译：Pertassis毒素通过抑制酸性鞘磷脂酶和激活磷酸肌醇3-激酶/蛋白激酶B通路来促进巨噬细胞存活

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

Apoptosis is an important mechanism involved in regulating the number of macrophages present at sites of inflammation. Several lines of evidence indicate that blocking macrophage apoptosis can increase atherosclerosis. We previously reported that oxidized LDL can inhibit apoptosis in cultured bone marrow-derived macrophages. We used pertussis toxin (PTX) to test whether G protein coupled receptors are activated by oxLDL. PTX is a bacterial toxin that inhibits G(i) activation by ADP-ribosylating the alpha subunit of Gi, preventing the subunit from interacting with receptors. Unexpectedly, we found that PTX by itself selectively blocks macrophage apoptosis in a dose-dependent manner. PTX acts in part by inhibiting acid sphingomyelinase activity which in turn prevents generation of ceramide, which is required for macrophage apoptosis. A G(i) activator peptide, mastoparan, increased ceramide levels in macrophage and induced apoptosis, but pre-treatment with PTX partially overrode mastoparan-induced apoptosis. The anti-apoptotic effect of PTX was found to require ADP-ribosylation. PTX failed to prevent A-SMase activation or apoptosis in macrophages lacking TLR4. The anti-apoptotic effect of PTX involved the same signaling pathways as those of oxidized LDL, in that both inhibited acid sphingomyelinase, and activated the phosphoinositide 3 kinase (PI3K)/protein kinase (PKB) pathway which leads to nuclear localization of the transcription factor NF kappa B and up-regulation of Bcl-X-L. These results indicate that G(i) proteins, TLR4, A-SMase and the PI3K/PKB pathway are crucial components for regulation of macrophage apoptosis. (c) 2007 Elsevier Inc. All rights reserved.
机译：凋亡是调节炎症位点处巨噬细胞数量的重要机制。有几条证据表明，阻断巨噬细胞凋亡可以增加动脉粥样硬化。我们以前曾报道过，氧化的LDL可以抑制培养的骨髓来源的巨噬细胞的凋亡。我们使用百日咳毒素（PTX）测试oxLDL是否激活了G蛋白偶联受体。 PTX是一种细菌毒素，可通过ADP核糖化Gi的α亚基来抑制G（i）激活，从而阻止该亚基与受体相互作用。出乎意料的是，我们发现PTX本身以剂量依赖性方式选择性阻断巨噬细胞凋亡。 PTX部分地通过抑制酸性鞘磷脂酶活性而起作用，而酸性鞘磷脂酶活性又阻止了巨噬细胞凋亡所必需的神经酰胺的产生。 G（i）激活肽，马索帕兰，增加巨噬细胞中的神经酰胺水平并诱导凋亡，但PTX预处理可部分覆盖马索帕兰诱导的细胞凋亡。发现PTX的抗凋亡作用需要ADP-核糖基化。 PTX未能阻止缺乏TLR4的巨噬细胞中A-SMase的活化或凋亡。 PTX的抗凋亡作用与氧化的LDL涉及相同的信号传导途径，即抑制酸性鞘磷脂酶并激活磷酸肌醇3激酶（PI3K）/蛋白激酶（PKB）途径，从而导致转录因子的核定位。 NFκB和Bcl-XL的上调。这些结果表明G（i）蛋白，TLR4，A-SMase和PI3K / PKB途径是调节巨噬细胞凋亡的关键组成部分。 （c）2007 Elsevier Inc.保留所有权利。

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