아밀로이드 베타에 의한 신경세포 사멸과 이에 대한 열충격 단백질 90의 세포 보호효과

초록

In the present study, we determined the protective mechanism of HSP90 against neuronal cell death induced by Aβ. For the evaluation of protective role of HSP90, we used human neuroblastoma SK-N-SH cell lines, examined AlamarBlue assay, Western blot analysis and immunofluorescence assay. Incubation of SK-N-SH cells with Aβ significantly induced neuronal cell death. However, HSP90 induced by mild heat shock could attenuate neuronal apoptosis in Aβ treated condition. To identify the role of HSP90, we determined localization of HSP90 in SK-N-SH cells. Interestingly, HSP90 was increased and localized in mitochondria as treatment of mild heat shock. Also, treatment or increase of HSP90 largely elevated level of Bcl-2 expression, whereas inhibition of HSP90 with HSP90 antisense oligonucleotide significantly decreased Bcl-2 expression. In contrast to Bcl-2, Bax expression was regulated independently by HSP90. Moreover, increase of HSP90 could attenuate collapse of mitochondrial membrane potential induced by Aβ. However, HSP90 antisense oligonucleotide largely increase breakdown of mitochondrial membrane potential induced by Aβ. These data suggest that HSP90 as chaperone protein significantly attenuates neuronal damage and protects neuroanl cells from neurotoxin such as Aβ.

키워드