title: The Aminopyridinol Derivative BJ-1201 Protects Murine Hippocampal Cells against Glutamate-Induced Neurotoxicity via Heme Oxygenase-1.
abstract: 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.
authors.affiliation: College of Pharmacy, Chosun University, Dong-gu, Gwangju 61452, Korea. dslee2771@chosun.ac.kr.
authors.forename: Dong-Sung
authors.initials: DS
authors.lastname: Lee
authors.affiliation: Department of Pharmacy, Hanyang University, Ansan 15588, Korea. tnam@hanyang.ac.kr.
authors.forename: Tae-Gyu
authors.initials: TG
authors.lastname: Nam
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 38541, Korea. jeongb@ynu.ac.kr.
authors.forename: Byeong-Seon
authors.initials: BS
authors.lastname: Jeong
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 42601, Korea. gsjeong@kmu.ac.kr.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
keywords: aminopyridinol HT22; aminopyridinol compound BJ-1201; heme oxygenase-1; neuroprotection; nuclear transcription factor erythroid-2 related factor 2