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

Abstract

The aim our study was to investigate protective effect of cobalt chloride (CoCl 2 ) 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 CoCl 2 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 CoCl 2 , 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 CoCl 2 but not with 17-AAG or IOX2 was associated with significant delay of the cell death induced by proteasome stress. CoCl 2 -mediated effect was consistent with inhibition of bortezomib-induced caspase 3 activation in the cells pre-treated with CoCl 2 . Despite established neuroprotective properties of Hsp70 our results do not provide strong evidence that the effect of CoCl 2 could be mainly attributed to the ability of CoCl 2 to induce expression of Hsp70 and other mechanisms have to be considered.