Depletion of intracellular zinc induces apoptosis of cultured hippocampal neurons through suppression of ERK signaling pathway and activation of caspase-3

Although Zinc depletion induces apoptosis in different cells and tissues, exact mechanism of this action of zinc depletion is not completely understood. In our previous study, the results suggested that the significant down-regulation of MEK/ERK signaling pathway was observed in zinc deficiency neurons. Here, we investigate whether, in hippocampal neurons, this increased rate of apoptosis induced by zinc depletion is the result of hypophosphorylation of ERK pathway. In this study, we found that NGF, ERK agonist, prevented neurons against TPEN-induced apoptosis, whereas TPEN-induced apoptosis was potentiated by U0126, inhibitors of ERK. Moreover, TPEN-induced caspase-3 activity was further increased by the pretreatment with U0126, but it was further decreased by the pretreatment with NGF. However, pretreatment of the cells with U0126 or NGF had no effect on the changes of Bcl-2 and Bax protein expression induced by zinc depletion. Thus, the results indicate that TPEN induces apoptosis of hippocampal neurons through inhibition of ERK and, in turn, activation of caspase-3