Quercetin ameliorates glutamate toxicity-induced decrease in parvalbumin expression and rise in intracellular calcium in HT22 cells

다국어 초록 (Multilingual Abstract)

Glutamate is the main excitatory neurotransmitter in neurons. However, excessive glutamate causes excitatory toxicity and increases intracellular calcium, leading to neuronal cell death. Parvalbumin is a calcium binding protein that regulates calcium homeostasis. Quercetin is a polyphenol that present in plant flavonoids and has neuroprotective effects against neurodegenerative diseases. We investigated whether quercetin regulates apoptosis through the expression of pavabumin in neuronal damage caused by glutamate. Glutamate was treated in hippocampal-derived cell lines, and quercetin and/or vehicle was treated 1 h before glutamate exposure. Cells were collected for experimental procedure 24 h after glutamate treatment. Glutamate exposure reduced cell viability and increased intracellular calcium concentration. Quercetin treatment alleviated these changes and exerts neuroprotective effects against glutamate toxicity. Moreover, glutamate exposure reduced parvalbumin expression and quercetin treatment attenuated the decrease in paralbumin expression by glutamate. These changes were confirmed using Western blot and immunocytochemical techniques. Glutamate treatment increased caspase-3 expression, quercetin attenuated this increase caused by glutamate toxicity in both parvalbumin siRNA transfected and non-transfected cells. However, the alleviative effect of quercetin was significant in non-transfected conditions. Caspase-3 is a representative apoptosis associated protein. Glutamate also induced a decrease in bcl-2 and increase in bax, quercetin alleviated glutamate-induced these changes. Bcl-2 expression in siRNA transfected cells was lower than in non-transfected cells. However, the expression of bax was high in siRNA transfected cells. Maintenance of proper calcium concentration is important for cell survival because calcium overload causes cell death. These results indicate that parvalbumin contributes to the prevention of apoptosis and quercetin modulates parvalbumin expression in glutamate-exposured cells. Maintenance of proper calcium concentration is important for cell survival because calcium overload causes cell death. Thus, the results of this study suggest that quercetin can perform neuroprotective function against glutamate toxicity by attenuating intracellular calcium overload and modulating bcl-2 family proteins and caspase-3 through regulating of pavalbumin expression. This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST) (NRF- 2018R1D1A1B07044074).