BJ-1103, 6-aminopyridin-3-ol skeletal compound, modulates neuroprotective and anti-neuroinflammatory effects in murine hippocampal and microglial cells via Nrf2-mediated heme oxygenase-1 expression. (3rd August 2016)

• Record Type: Journal Article
• Authors: Lee, Dong-Sung; Nam, Tae-Gyu; Jeong, Byeong-Seon; Jeong, Gil-Saeng
• Is Part Of: Neuroscience letters. Volume 627(2016)
• Page Start: 42
• Page End: 50
• Publication Date: 2016-08-03
• Subjects: HO-1 heme oxygenase-1 -- Nrf2 nuclear transcription factor erythroid-2 related factor 2 -- AREs antioxidant response elements -- ROS reactive oxygen species -- NO nitric oxide -- PGE 22prostaglandin E2 -- Keap-1 Kelch-like ECH-associated protein-1 -- MAPKs mitogen-activated kinase; 6-Aminopyridin-3-ol skeletal BJ-1103 -- Heme oxygenase-1 -- Nuclear transcription factor erythroid-2 related factor 2 -- Hippocampal HT22 -- Microglial BV2; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2016.05.056
• Languages: English
• ISSNs: 0304-3940

Abstract

Graphical abstract: Highlights: BJ-1103 is a 6-aminopyridin-3-ol skeletal compound. BJ-1103 inhibits neurotoxicity or neuroinflammation. BJ-1103 can protect HT22 cells against glutamate-induced cell cytotoxicity. BJ-1103 increased HO-1 expression and activity via Nrf2 translocation. BJ-1103 may have good therapeutic agent against neurodegenerative diseases. Abstract: BJ-1103, as a 6-aminopyridin-3-ol skeletal compound, was originally developed as an antioxidant against free radicals and oxidative stress was prepared from pyridoxine·HCl by the reported procedure. In the present study, we examined the effect of BJ-1103 on neuroprotection and neuroinflammation. Our data showed that BJ-1103 can protect HT22 cells against glutamate-induced cell cytotoxicity. And, BJ-1103 also inhibited LPS-induced inflammatory action. In addition, BJ-1103-induced heme oxygenase-1 (HO-1) expression and elevated HO-1 activities in the two cell lines studied. Additionally, BJ-1103 treatment induced nuclear transcription factor erythroid-2 related factor 2 (Nrf2) and increased the promoter activity of antioxidant response elements (AREs). We have demonstrated using the Nrf2 siRNA, HO inhibitor or HO-1 siRNA that BJ-1103 suppressed neurotoxicity and neuroinflammation through the Nrf2-mediated HO-1 expression. These results demonstrated that BJ-1103 may have good therapeutic agent against neurodegenerative diseases that are induced by oxidative stress and neuroinflammation.