Expression of stress-response ATF3 is mediated by Nrf2 in astrocytes.
Activating Transcription Factor 3 (ATF3), a member of the ATF/CREB family, is induced rapidly by various stresses. Its induction mechanism and role in response to changes in cellular redox status, however, have not been elucidated. Here, we found that NF-E2-related factor 2 (Nrf2), a transcription factor known to bind to antioxidant response element (ARE) in promoters, transcriptionally upregulated ATF3 expression in astrocytes. Treatment with Nrf2 activators and oxidants provoked ATF3 induction in astrocytes, whereas its expression was reduced in Nrf2-depleted cells. We further demonstrated that the consensus ARE in the ATF3 promoter is critical for Nrf2-mediation by promoter analyses using an ATF3 promoter-driven luciferase construct and a chromatin immunoprecipitation assay. In addition, we found that Nrf2-dependent ATF3 induction contributed to the antioxidative and cytoprotective functions of Nrf2 in astrocytes. Taken together, our findings suggest that ATF3 is a new target for Nrf2 and has a cytoprotective function in astrocytes.
Kim
Kyu-Han
KH
NeuroVascular Coordination Research Center, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
Jeong
Jae-Yeon
JY
Surh
Young-Joon
YJ
Kim
Kyu-Won
KW
D051700:Activating Transcription Factor 3 / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001665:Binding Sites; D002478:Cells, Cultured; D019610:Cytoprotection; D006801:Humans; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D020218:Response Elements
C490449:ATF3 protein, human; D051700:Activating Transcription Factor 3; D051267:NF-E2-Related Factor 2; D016877:Oxidants