K141N突变型小分子热休克蛋白22轴突转运障碍及其在CMT2L发病机制中的作用  

Roles of axonal transport affected by K141N mutant HSP22 in the pathogenesis of CMT2L

作　　者：张付峰[1] 卢晓琴[2] 周亚芳[1] 沈璐[3] 江泓[3] 严新翔[3] 唐北沙[3] 

机构地区：[1]中南大学湘雅医院老年科,长沙410008 [2]中南大学湘雅医院 急诊科,长沙410008 [3]中南大学湘雅医院神经内科,长沙410008

出　　处：《中华医学杂志》2012年第7期496-498,共3页National Medical Journal of China

基　　金：国家自然科学基金（30900805）;教育部博士点新教师青年基金（20100162120054）;中南大学自由探索项目（201012200132）

摘　　要：目的 比较野生型和K141N突变型小分子热休克蛋白22（ HSP22）在原代培养小鼠皮质神经元轴突中的转运情况.方法 将构建好的含有人类野生型和K141N突变型HSP22基因的质粒（pCAGGS-HA-wtHSP22和pCAGGS-HA-K141N HSP22）分别与pEGFP-N1共转染小鼠皮质神经元,转染后观察野生型和K141N突变型HSP22蛋白在小鼠皮质神经元轴突内的转运情况,分析野生型和K141N突变型HSP22蛋白在轴突内的转运距离.结果 野生型HSP22蛋白在皮质神经元内被转运到轴突的最远端[转运距离（637±117）μm],K141N突变型HSP22蛋白仅被转运到轴突的近端[转运距离（29±12）μm],野生型和K141N突变型HSP22蛋白在轴突中被转运的距离差异具有统计学意义.结论 K141N突变型HSP22蛋白在轴突内的转运障碍可能在CMT2L型的发病中起着重要作用.Objective To compare the axonal transport of wild-type （WT） and K141N mutant HSP22 in transfected primary cultured cortical neurons.Methods The plasmid （pCAGGS-HA-wtHSP22 or pCAGGS-HA-K141NHSP22） with WT or K141N mutant HSP22 gene and a GFP-expressing plasmid （ pEGFP-N1 ） were co-transfected respectively into primary cultured cortical neurons.The axonal transport of WT and K141N mutant HSP22 was observed.And the distance traveled by WT and K141N mutant HSP22 was analyzed.Results The WT HSP22 was transported within axons and uniformly present throughout the entire length of axons.K141N mutant HSP22 failed to be transported to the same extent and was present only in cell body and proximal portion of axons.Analysis of distance traveled revealed that WT HSP22 traveled significantly further than the K141N mutant HSP22.Conclusion The axonal transport of K141N mutant HSP22 may play an important role in the pathogenesis of CMT2L.

关 键 词：夏科-马里-图斯病 热休克蛋白类 小分子 轴突运输 

分 类 号：R746[医药卫生—神经病学与精神病学]