...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Nucleus >LMNA missense mutations causing familial partial lipodystrophy do not lead to an accumulation of prelamin A
【24h】

LMNA missense mutations causing familial partial lipodystrophy do not lead to an accumulation of prelamin A

机译：导致家族性部分脂肪营养不良的LMNA错义突变不会导致前醇溶蛋白A的积累

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A variety of missense mutations in LMNA (the gene for lamin C and prelamin A) cause familial partial lipodystrophy (FPLD), a disease associated with reduced adipose tissue, particularly in the limbs. Several studies have reported that fibroblasts from FPLD subjects have an accumulation of prelamin A. Those findings were intriguing but also perplexing because many of the LMNA missense mutations associated with lipodystrophy are located in sequences distant from the sequences required for the farnesylation of prelamin A and ZMPSTE24-mediated conversion of prelamin A to mature lamin A. Here, we revisited the issue of prelamin A accumulation in the setting of FPLD mutations. We used western blots with lamin A/C antibodies and prelamin A–specific monoclonal antibodies to assess prelamin A levels in wild-type fibroblasts and fibroblasts carrying LMNA mutations associated with lipodystrophy (R482W, I299V, C591F, T528M). None of the mutant fibroblasts exhibited an accumulation of prelamin A. Also, the amount of prelamin A accumulation in response to lopinavir (an inhibitor of ZMPSTE24) was similar in wild-type and mutant fibroblasts. Thus, the LMNA lipodystrophy mutations that we examined did not lead to prelamin A accumulation, nor did they render those cells more susceptible to prelamin A accumulation when ZMPSTE24 was inhibited by lopinavir.
机译：LMNA（lamin C和prelamin A的基因）中的多种错义突变会导致家族性部分脂肪营养不良（FPLD），这是一种与脂肪组织减少有关的疾病，特别是在四肢。几项研究报告说，来自FPLD受试者的成纤维细胞中积累了prelaminA。这些发现既有趣又令人困惑，因为许多与脂营养不良相关的LMNA错义突变位于与prelamin法尼基化所需序列相距较远的序列中。 A和ZMPSTE24介导的前层蛋白A到成熟层粘蛋白A的转化。在这里，我们再次探讨了在FPLD突变情况下前层蛋白A积累的问题。我们使用了带有lamin A / C抗体和prelamin A特异性单克隆抗体的western印迹来评估野生型成纤维细胞和带有与脂营养不良相关的突变的成纤维细胞（R482W，I299V，C591F，T528M）中的prelamin A水平。突变的成纤维细胞均未显示出prelamin A的积累。此外，在野生型和突变的成纤维细胞中，响应洛匹那韦（ZMPSTE24的抑制剂）而产生的prelamin A的积累量相似。因此，当洛匹那韦抑制ZMPSTE24时，我们检查的LMNA脂肪营养不良突变不会导致prelamin A积累，也不会使这些细胞更容易受到prelamin A积累的影响。

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