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Yu, Ah-Ran,Jeong, Yeon Ju,Hwang, Chi Yeon,Yoon, Kyung-Sik,Choe, Wonchae,Ha, Joohun,Kim, Sung Soo,Pak, Youngmi Kim,Yeo, Eui-Ju,Kang, Insug Elsevier 2019 NeuroToxicology Vol.71 No.-
<P><B>Abstract</B></P> <P>α-Naphthoflavone (αNF) is a prototype flavone, also known as a modulator of aryl hydrocarbon receptor (AhR). In the present study, we investigated the molecular mechanisms of αNF-induced cytotoxic effects in HT22 mouse hippocampal neuronal cells. αNF induced apoptotic cell death via activation of caspase-12 and -3 and increased expression of endoplasmic reticulum (ER) stress-associated proteins, including C/EBP homologous protein (CHOP). Inhibition of ER stress by treatment with the ER stress inhibitor, salubrinal, or by CHOP siRNA transfection reduced αNF-induced cell death. αNF activated mitogen-activated protein kinases (MAPKs), such as p38, JNK, and ERK, and inhibition of MAPKs reduced αNF-induced CHOP expression and cell death. αNF also induced accumulation of reactive oxygen species (ROS) and an antioxidant, N-acetylcysteine, reduced αNF-induced MAPK phosphorylation, CHOP expression, and cell death. Furthermore, αNF activated c-Src kinase, and inhibition of c-Src by a kinase inhibitor, SU6656, or siRNA transfection reduced αNF-induced ROS accumulation, MAPK activation, CHOP expression, and cell death. Inhibition of AhR by an AhR antagonist, CH223191, and siRNA transfection of AhR and AhR nuclear translocator reduced αNF-induced AhR-responsive luciferase activity, CHOP expression, and cell death. Finally, we found that inhibition of c-Src and MAPKs reduced αNF-induced transcriptional activity of AhR. Taken together, these findings suggest that αNF induces apoptosis through ER stress via c-Src-, ROS-, MAPKs-, and AhR-dependent pathways in HT22 cells.</P> <P><B>Highlights</B></P> <P> <UL> <LI> α-Naphthoflavone (αNF), an arylhydrocarbon receptor modulator (AhR), induces apoptosis in HT22 hippocampal neuronal cells. </LI> <LI> ER stress plays a role in αNF-induced apoptosis. </LI> <LI> The c-Src-, ROS-, MAPK-, and AhR-dependent pathways are implicated in αNF-induced ER stress and apoptosis. </LI> <LI> The AhR nuclear translocator-dependent genomic pathway also mediates αNF-induced ER stress and apoptosis. </LI> </UL> </P>
Choi, Jae Sue,Han, Yu Ran,Byeon, Jeong Su,Choung, Se-Young,Sohn, Hee Sook,Jung, Hyun Ah Pharmaceutical Society of Great Britain 2015 Journal of pharmacy and pharmacology Vol.67 No.8
<P>Fucosterol is the primary sterol found in brown algae. Recently, considerable interest has been generated regarding fucosterol due to its potential antioxidant, anti-inflammatory and antidiabetic effects. The aim of this study was to investigate the protective effects of fucosterol on tert-butyl hydroperoxide (t-BHP)- and tacrine-induced oxidative stress in HepG2 cells.</P>