Germinated brown rice protects against glutamate toxicity in HT22 hippocampal neurons through the jnk-mediated apoptotic pathway via the GABAA receptor.

Abstract

The anti-apoptosis effect of germinated brown rice (GBR) focusing on differentiated HT22 cells results in improved nutritional values after the germination process of GBR which contains total phenolic compounds and γ-aminobutyric acid (GABA). Cell death induced by 5mM glutamate was investigated for 24h to determine whether GBR mediates cell death through GABA receptors by using antagonists. The results showed that GBR (100µg/ml) suppressed glutamate-induced cytotoxicity and caused arrest at the G1/S phase of the cell cycle in differentiated HT22 cells. Furthermore, GBR significantly decreased the expression level of c-Jun, while its active form, p-c-Jun, is the downstream product of the JNK-mediated apoptotic pathway and causes subsequent cell death. In addition, bicuculline (12.5nM), a GABAA antagonist, could eliminate GBR effects, but phaclofen (1mM), a GABAB antagonist, could not. Surprisingly, GBR exhibited a better neuroprotective effect than a pure commercial GABA compound (0.115µM). These results indicated that GBR possessed high anti-apoptotic activity and inhibited cell death in differentiated HT22 cells by perturbing re-entry of the cell cycle and apoptosis via the GABAA receptor. Hence, GBR could be further used as a valuable nutritional compound to prevent apoptosis-induced neurodegenerative diseases.