Nagao Y, Ishiguro H, Nukina N
Laboratory for CAG Repeat Diseases, Brain Science Institute, RIKEN, The Institute of Physical and Chemical Research, Wako, Saitama, Japan.
Biochim Biophys Acta. 2000 Oct 18;1502(2):247-56. doi: 10.1016/s0925-4439(00)00047-8.
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.
亨廷顿舞蹈症（HD）由一个拥有67个外显子的大基因IT15的外显子1中CAG重复序列扩增引起。仅从外显子1翻译出具有扩展的聚谷氨酰胺序列的亨廷顿蛋白截短N端肽的转基因小鼠会出现类似于亨廷顿舞蹈症的症状。在本研究中，使用细菌系统（大肠杆菌）来表达从HD基因外显子1翻译出的亨廷顿蛋白截短肽。在用具有扩展聚谷氨酰胺序列的肽诱导后观察到细菌死亡，并且通过免疫印迹在这种大肠杆菌的匀浆中检测到十二烷基硫酸钠（SDS）可溶性肽和不溶性聚集物。通过向培养基中添加二甲基亚砜（DMSO）或甘油，大肠杆菌死亡部分减少，随之匀浆中聚集物减少，SDS可溶性肽增加。这些结果表明，DMSO和甘油可能通过充当化学伴侣来降低具有扩展聚谷氨酰胺序列的亨廷顿蛋白的毒性。
