期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 30, 期 8, 页码 -出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2020.127058
关键词
Isoliquirtigenin; Glutamate induced neurotoxicity; HT22 mouse hippocampal neuronal cells; MAPKs; AIF
资金
- KIST Institutional Program [2Z06260]
- National Research Council of Science Technology [CRC-15-04-KIST]
- Ministry of Oceans and Fisheries, Korea [20170488]
- National Research Foundation of Korea [2Z06260] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Glutamate-induced neurotoxicity is characterized by cellular Ca2+ uptake, which is upstream of reactive oxygen species (ROS)-induced apoptosis signaling and MAPKs activation. In the present study, we synthesized isoliquiritigenin analogs with electron-donating and electron-withdrawing functional groups. These analogs were evaluated for neuroprotective effect against glutamate-induced neurotoxicity in HT22 cells. Among these analogs, compound BS11 was selected as a potent neuroprotective agent. Cellular Ca2+ concentration, ROS level, MAPKs activation and AIF translocation to the nucleus were increased upon treatment with 5 mM glutamate. In contrast, we identified that compound BS11 reduced the cellular Ca2+ concentration and ROS level upon glutamate exposure. Western blot analysis showed that MAPK activation was decreased by treatment with compound BS11. We further identified that cotreatment of compound BS11 and glutamate inhibited translocation of AIF to the nucleus.
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