Glutamate에 유도된 SH-SY5Y 세포에서의 미토콘드리아 손상, 세포 자연사 그리고 NLRP3 inflammasome 활성에 대한 KHG21834의 억제 효과

Abstract

New compounds were screened to develop effective drugs against glutamate-induced toxicity. The present study assessed the effects of the novel thiazole derivative KHG21834 against glutamate-induced toxicity in human neuroblastoma SH-SY5Y cell cultures. Treatment of SH-SY5Y cells with KHG21834 significantly protected cells against glutamate-induced toxicity in a dose-dependent manner, with an optimum concentration of 50 μM. KHG21834 protected SH-SY5Y cells against glutamate toxicity by suppressing glutamate-induced oxidative stress by 50%. KHG21834 also attenuated glutamate-induced intracellular Ca2+ influx, mitochondrial membrane potential and ATP level reductions. Furthermore, KHG21834 efficiently reduced glutamate-induced ER stress and NLRP3 inflammasome activation (59% and 65% of glutamate group, respectively). In addition, KHG21834 effectively attenuated glutamate-induced levels of Bax, Bcl-2, cleaved caspase-3, p-p38, p-JNK proteins, and TUNEL positive cells. To our knowledge, this is the first study showing that KHG21834 can effectively protect SH-SY5Y cells against glutamate toxicity, suggesting that this compound may be a valuable therapeutic agent for the treatment of glutamate toxicity.