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KHG21834 attenuates glutamate-induced mitochondrial damage, apoptosis, and NLRP3 inflammasome activation in SH-SY5Y human neuroblastoma cells.
Yang, Seung-Ju; Han, A Reum; Kim, Eun-A; Yang, Ji Woong; Ahn, Jee-Yin; Na, Jung-Min; Cho, Sung-Woo.
Afiliación
  • Yang SJ; Department of Biomedical Laboratory Science, Konyang University, Daejeon, 35365, South Korea.
  • Han AR; Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
  • Kim EA; Department of Biomedical Laboratory Science, Konyang University, Daejeon, 35365, South Korea.
  • Yang JW; Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
  • Ahn JY; Department of Molecular Cell Biology, Center for Molecular Medicine, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Suwon, 16419, South Korea.
  • Na JM; Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 05505, South Korea.
  • Cho SW; Department of Biochemistry and Molecular Biology, University of Ulsan College of Medicine, Seoul, 05505, South Korea. Electronic address: swcho@amc.seoul.kr.
Eur J Pharmacol ; 856: 172412, 2019 Aug 05.
Article en En | MEDLINE | ID: mdl-31129157
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 mitochondrial membrane potential, ATP level reductions, and intracellular Ca2+ influx. 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apoptosis / Ácido Glutámico / Benzotiazoles / Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR / Mitocondrias / Neuroblastoma Límite: Humans Idioma: En Revista: Eur J Pharmacol Año: 2019 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Apoptosis / Ácido Glutámico / Benzotiazoles / Inflamasomas / Proteína con Dominio Pirina 3 de la Familia NLR / Mitocondrias / Neuroblastoma Límite: Humans Idioma: En Revista: Eur J Pharmacol Año: 2019 Tipo del documento: Article País de afiliación: Corea del Sur Pais de publicación: Países Bajos