The protective role of HSP90 against 8-hydroxykynurenine-induced neuronal apoptosis

3-Hydroxykynurenine (3HK), an endogenous metabolite of tryptophan in the ky nurenine pathway, is a potential neurotoxin in several neurodegenerative di sorders. Stabilizing protein structure, heat shock proteins (HSPs) have div erse roles as molecular chaperones to mediate stress tolerance. In the pres ent study, we investigated the possible protective role of HSPs against 3HK induced neuronal cell death. Here we report that 3HK induced in a dose- an d time-dependent manner neuronal cell death in neuroblastoma SK-N-SH cells. The cell death showed characteristic apoptotic features such as cell shrin kage, plasma membrane blebbing, chromatin condensation, and nuclear condens ation and fragmentation. Furthermore, SK-N-SN cells were protected from 3HK induced cytotoxicity by prior elevation of HSPs expression. Our results sh ow that the protective effect was abolished by HSP90 anti-sense oligonucleo tides while not by HSP27 and HSP70 anti-sense oligonucleotides. Also, our r esult shows that HSP90 effectively inhibits caspases activities leading to the apoptosis. These results suggest that 3HK induces apoptosis in neurobla stoma SK-N-SN cells and that BSP90 is major contributing protein component of protection against 3HK induced apoptosis. (C) 2001 Academic Press.