Protective Role And Mechanism Study For Peroxiredoxin V In HT22 Cell Apoptosis Induced By Glutamate

Peroxiredoxin(Prx) V belongs to Peroxiredoxon family, and functions in reducing cellular ROS and peroxyntitrites. Previous studies have revealed that the Prx V protein not only has peroxidase activities, but also plays a role in regulating the cell proliferation, differentiation, apoptosis, and aging. Alzheimer’s disease(AD) is a neurodegenerative disorder that is characterized by the progressive decline of memory, cognitive functions, and changes in behavior and personality. Loss of hippocampus neurons is one of the major pathological hallmarks of AD. In recent years, the protective roles of Prxs in the pathogenesis of AD have been reported. However, the role of Prx V in glutamate-induced neuronal apoptosis remains to be studied.In the present study, we examined the protective function of Prx V on glutamate-induced neuronal apoptosis in mock and Prx V knockdown HT22 mouse hippocampus neuronal cells. We started with examining the effect of glutamate on Prx V protein expression in HT22 cells. Our results showed that upon glutamate stimulation, similar to the patterns of apoptosis level and celluar ROS levels, Prx V protein expression was up-regulated in a time- and dose- dependent manner in HT22 cells. To investigate the roles of Prx V in glutamate induced apoptosis in HT22 cells, we prepared HT22 stable cell line with an sh-RNA mediated expression knockdown of Prx V. According to the MTT assay results, the expression knockdown of Prx V significantly increased the HT22 cell death induced by glutamate than the mock sh-RNA. Results showed that ERK phosphorylation and cleavage caspase 3 expression were significantly up-regulated in glutamate-stimulated Prx V knockdown HT22 cells, while other molecules(JNK, p38, Bcl-2, Bad) did not change.In conclusion, the knockdown of Prx V accelerated the glutamate-induced apoptosis in HT22 cells, possibly via the regulation of ERK pathway. Our findings would provide a novel therapeutic target for the glutamate-induced hippocampal neuronal apoptosis.