The Aminopyridinol Derivative BJ-1201 Protects Murine Hippocampal Cells against Glutamate-Induced Neurotoxicity via Heme Oxygenase-1

• Main Authors: Dong-Sung Lee, Tae-Gyu Nam, Byeong-Seon Jeong, Gil-Saeng Jeong
• Format: Article
• Language: English
• Published: MDPI AG 2016-05-01
• Series: Molecules
• Subjects: aminopyridinol compound BJ-1201; neuroprotection; aminopyridinol HT22; heme oxygenase-1; nuclear transcription factor erythroid-2 related factor 2
• Online Access: http://www.mdpi.com/1420-3049/21/5/594

Glutamate is the major excitatory neurotransmitter in the brain. It can cause neuronal cell damage in the context of oxidative stress. BJ-1201 is a derivative of the compound aminopyridinol, which is known for its antioxidant activity. In this study, we examined the effect of BJ-1201, a 6-(diphenylamino)-2,4,5-trimethylpyridin-3-ol compound, on neuroprotection in HT22 cells. Our data showed that BJ-1201 can protect HT22 cells against glutamate-induced cell cytotoxicity. In addition, BJ-1201 upregulated heme oxygenase-1 (HO-1) to levels comparable to those of the CoPP-treated group. BJ-1201 treatment induced phosphorylation of JNK, but not p38-MAPK or ERK. It also increased the signal in the reporter assay based on β-galactosidase activity driven by the nuclear transcription factor erythroid-2 related factor 2 (Nrf2) promoter harboring antioxidant response elements (AREs) and induced the translocation of Nrf2. These results demonstrate that BJ-1201 may be a good therapeutic platform against neurodegenerative diseases induced by oxidative stress.