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General Physiology and Biophysics Vol.37, No.6, p.667–676, 2018 |
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Title: Cobalt chloride affects the death of SH-SY5Y cells induced by inhibition of ubiquitin proteasome system. Role of heat shock protein 70 and caspase 3 | ||
Author: S. Saksonová, M. Brodňanová, K. Dibdiaková, I. Pilchová, K. Klačanová, J. Hatok, P. Račay | ||
Abstract: The aim our study was to investigate protective effect of cobalt chloride (CoCl2) in the model of proteasome stress of neuroblastoma SH-SY5Y cells induced by bortezomib, an inhibitor of 26S proteasome. We have focused our interests on Hsp70 and activation of caspase 3. Finally, we have compared the effect of CoCl2 with an effect of the pre-treatment of the cells with 17-AAG, an inhibitor of Hsp90 that is capable to induce expression of Hsp70, or with IOX2, an inhibitor of isoform 2 of prolyl hydroxylase that increases stability of hypoxia‑inducible factor 1α (HIF1α). Pre-treatment of SH-SY5Y cells for 24 h with CoCl2, at concentrations of 150 or 250 µmol/l, and with 17-AAG at concentration 1 µmol/l but not with IOX2 at concentration 100 µmol/l, was associated with significantly increased expression of Hsp70. We have shown that pre-treatment of SH-SY5Y cells with CoCl2 but not with 17-AAG or IOX2 was associated with significant delay of the cell death induced by proteasome stress. CoCl2-mediated effect was consistent with inhibition of bortezomib-induced caspase 3 activation in the cells pre-treated with CoCl2. Despite established neuroprotective properties of Hsp70 our results do not provide strong evidence that the effect of CoCl2 could be mainly attributed to the ability of CoCl2 to induce expression of Hsp70 and other mechanisms have to be considered. |
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Keywords: Neuroprotection, Ubiquitin proteasome system, Cobalt chloride, Heat shock proteins, Caspase 3 | ||
Published online: 28-Nov-2018 | ||
Year: 2018, Volume: 37, Issue: 6 | Page From: 667, Page To: 676 | |
doi:10.4149/gpb_2018022 |
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