Effects of sertraline on the cell viability and expression of tyrosine hydroxylase and phosphorylated ERK1/2 in NGF-induced PC12 cells

Abstract

Objective To investigate the effect of sertraline on the viability and the expression of tyrosine hydroxylase (TH) and phosphorylated ERK1/2 in NGF-induced rat pheochromocytoma (PC12) cells.Methods NGF-induced PC12 cells were pretreated or directly treated with different concentrations of sertraline for 24 or 48 hours and the pretreated groups were then subjected to serum withdrawal condition. Then cell viability was determined by the cell counting Kit-8 (CCK-8). The expression of Tyrosine hydroxylase (TH) and pERK1/2in NGF-induced PC12 cells was determined by immunohistochemistry and western blot respectively. Results The viability of NGF-induced PC12 was improved after administration with sertra]ine. After 24h sertraline administration, the cells activity of PC 12 cells at 20μM ( 1.32 ± 0. 11 ) , 10μM ( 1. 17 ± 0.05 ) of direct effect, and 20μM ( 1.15 ±0.11 ) of protect effect increased dramatically as compared with control group. But high dose ( 50μM )sertraline express high toxic effect to PC12 cells. The expression of TH was increased by sertraline 20 μM at both 24h(ratio of TH/β-actin = 1.27 ±0.05) and 48h(ratio of TH/β-actin = 1. 23 ±0.08) compare with control group,and the expression of pERK1/2 also increased dramatically by sertraline 20 μM at both 24h (ratio of (pERK1/2)/β-actin = 1.41±0.05) and 48h( ratio of (pERK1/2)/β-actin = 1.40 ±0.06) compare with control group(P＜0. 01, P ＜ 0. 05). Immunohistochemistry showed similar results. Conclusion These data suggest that the neuroprotective effect of sertraline may play an important role in depression therapy, and this effect might be mediated by TH and pERK1/2 up-regulation. Key words: PC12 cells; Sertraline; Hydroxylase; pERK1/2