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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >DMSO and glycerol reduce bacterial death induced by expression of truncated N-terminal huntingtin with expanded polyglutamine tracts
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DMSO and glycerol reduce bacterial death induced by expression of truncated N-terminal huntingtin with expanded polyglutamine tracts

机译:DMSO和甘油减少了具有扩展的聚谷氨酰胺束的截短的N末端亨廷顿蛋白表达诱导的细菌死亡

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摘要

Huntington's disease (HD) is caused by CAG repeat expansion in exon 1 of a large gene, IT15, possessing 67 exons. Transgenic mice expressing a truncated N-terminal peptide of huntingtin with an expanded polyglutamine tract translated only from exon 1 develop symptoms similar to Huntington's disease. In the present study, a bacterial system (Escherichia coli) was used to express truncated peptides of huntingtin translated from exon 1 of the HD gene. Bacterial death was observed after the induction of peptides with expanded polyglutamine tracts, and both sodium dodecyl sulfate (SDS)-soluble peptides and insoluble aggregated material were detected by immunoblotting in the homogenates of such E. coli. E. coli death was partially reduced by the addition of dimethylsulfoxide (DMSO) or glycerol to the medium, with a consequent decrease in aggregated material and an increase in SDS-soluble peptide in the homogenate. These results suggest that DMSO and glycerol may decrease the toxicity of huntingtin with expanded polyglutamine tracts by acting as chemical chaperones.
机译:亨廷顿舞蹈病(HD)是由大基因IT15的外显子1中的CAG重复扩增引起的,该基因具有67个外显子。表达具有仅从外显子1翻译的扩增的聚谷氨酰胺束的亨廷顿蛋白的截短的N-末端肽的转基因小鼠产生类似于亨廷顿氏病的症状。在本研究中,细菌系统(大肠杆菌)用于表达从HD基因第1外显子翻译的亨廷顿蛋白的截短肽。在用扩展的聚谷氨酰胺束诱导肽后观察到细菌死亡,并且通过在此类大肠杆菌的匀浆中进行免疫印迹来检测十二烷基硫酸钠(SDS)可溶性肽和不溶性聚集物质。通过向培养基中添加二甲亚砜(DMSO)或甘油,可部分减少大肠杆菌的死亡,从而减少聚集物质,并增加匀浆中SDS可溶性肽的含量。这些结果表明,DMSO和甘油可通过充当化学分子伴侣来降低具有扩展的聚谷氨酰胺束的亨廷顿蛋白的毒性。

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