HSP40 and HSP70 inhibit the accumulation and toxicity of mutant huntingtin in N2a cells / 解剖学报

Objective To study the effect of heat shock protein 40(HSP40) and heat shock protein 70(HSP70) on the aggregate formation of mutant huntingtin (htt) and its toxicity in N2a cells. Methods The effect of the over-expression of HSP40 and HSP70 alone or co-over-expression of them on aggregate formation of transfected mutant htt (containing 150 glutamine repeats, 150Q) in N2a cells was detected by fluorescence microcopy and Western blotting. Cell viabilities were detected by MTT assay. Reactive oxygen species (ROS) production was detected by colorimetric method. Results The over-expression of HSP40 and HSP70 alone, especially the co-over-expression of them, dramatically decreases the formation of 150Q htt aggregates in N2a cells. The numbers of aggregates in each group are as follows ( n = 1 000): about 50% in the group of 150Q htt-expressing alone, about 12% in the group of over-expression of HSP40, about 15% in the group of over-expression of HSP70, about 5% in the group of co-over-expression of HSP40 and HSP70. The result of MTT assay shows that the over-expression of HSP40 and HSP70 alone, especially the co-over-expression of them, dramatically increases cell viabilities ( P<0.01, n =3) and reduces the production of ROS ( P<0.01, n =3). Conclusion HSP40 and HSP70 can increase cell viabilities of 150Q N2a cells via inhibiting the aggregates formation of mutant huntingtin and reducing oxidative stress.

Impaired function of pancreatic ? cells in the R6/2 transgenic mouse model of Huntington's disease / 中国病理生理杂志

AIM:To study the function of pancreatic ? cells in the R6/2 transgenic mouse of Huntington's disease(HD),and to elucidate the pathogenetic mechanisms underlying diabetes mellitus in transgenic mice of HD. METHODS:By using the R6/2 transgenic mouse model of HD,fasting blood glucose and fasting insulin concentration in plasma of normal and HD mice were detected. Further,HE staining and immunofluorescence technique were used for morphometric analysis of islets in normal and HD mice. RESULTS:In contrast to normal mouse,R6/2 HD mouse showed hyperglycemia and hypoinsulinemia in fasting state. Pancreatic islets morphology showed that islets atrophied and cell number decreased in HD mouse. Poor functional index was observed in these mice,but insulin resistance index was normal. CONCLUSION:Impaired function of pancreatic cells may be the key factor contributing to the pathogenesis of diabetes in the R6/2 transgenic mouse model of HD.