• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Cholesterol-enriched membrane microdomains are needed for insulin signaling and proliferation in hepatic cells
【24h】

Cholesterol-enriched membrane microdomains are needed for insulin signaling and proliferation in hepatic cells

机译：肝细胞中胰岛素信号传导和增殖需要富含胆固醇的膜微膜

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

Hepatocyte proliferation during liver regeneration is a well-coordinated process regulated by the activation of several growth factor receptors, including the insulin receptor (IR). The IR can be localized in part to cholesterol-enriched membrane microdomains, but the role of such domains in insulin-mediated events in hepatocytes is not known. We investigated whether partitioning of IRs into cholesterol-enriched membrane rafts is important for the mitogenic effects of insulin in the hepatic cells. IR and lipid rafts were labeled in HepG2 cells and primary rat hepatocytes. Membrane cholesterol was depleted in vitro with metyl-?cyclodextrin (M睠D) and in vivo with lovastatin. Insulin-induced calcium (Ca~(2+)) signals studies were examined in HepG2 cells and in freshly isolated rat hepatocytes as well as in whole liver in vivo by intravital confocal imaging. Liver regeneration was studied by 70% partial hepatectomy (PH), and hepatocyte proliferation was assessed by PCNA staining. A subpopulation of IR was found in membrane microdomains enriched in cholesterol. Depletion of cholesterol from plasma membrane resulted in redistribution of the IR along the cells, which was associated with impaired insulin-induced nuclear Ca~(2+) signals, a signaling event that regulates hepatocyte proliferation. Cholesterol depletion also led to ERK1/2 hyper-phosphorylation. Lovastatin administration to rats decreased hepatic cholesterol content, disrupted lipid rafts and decreased insulin-induced Ca~(2+) signaling in hepatocyles, and delayed liver regeneration after PH. Therefore, membrane cholesterol content and lipid rafts integrity showed to be important for the proliferative effects of insulin in hepatic cells.
机译：肝脏再生期间的肝细胞增殖是通过激活若干生长因子受体（包括胰岛素受体（IR）调节的良好协调的方法。 IR可以部分地分为富含胆固醇的膜微瘤，但是这种域在肝细胞中的胰岛素介导的事件中的作用是未知的。我们研究了IRS是否进入胆固醇型膜筏中的分区对于肝细胞中胰岛素的促致动作用是重要的。 IR和脂质筏在HepG2细胞和原代大鼠肝细胞中标记。膜胆固醇在体外耗尽，含有聚合物 - α环糊精（M = D）和洛伐他汀体内。在HepG2细胞中检查胰岛素诱导的钙（Ca〜（2+））信号，并在新鲜分离的大鼠肝细胞中以及通过球衣共聚焦成像在体内的整个肝脏中。通过70％的部分肝切除术（pH）研究了肝脏再生，并通过PCNA染色评估肝细胞增殖。在胆固醇中富集的膜微膜发现IR亚亚亚亚亚。来自血浆膜的胆固醇的耗竭导致沿着细胞的再分布，这与胰岛素诱导的核Ca〜（2+）信号受损，这是调节肝细胞增殖的信号传导事件。胆固醇耗尽也导致ERK1 / 2高磷酸化。 Lovastatin给大鼠的给药降低肝胆胆固醇含量，破坏脂质筏和胰岛素诱导的Ca〜（2+）信号传导，在pH后延迟肝再生。因此，膜胆固醇含量和脂肪筏完整性表明对于肝细胞中胰岛素的增殖作用是重要的。

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