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ID 114572
著者
Mimura, Junsei Hirosaki University
Inose-Maruyama, Atsushi Hirosaki University|Tohoku Medical and Pharmaceutical University
Taniuchi, Shusuke The University of Tokushima
Kosaka, Kunio Nagase & Co. Ltd.
Yoshida, Hidemi Hirosaki University
Yamazaki, Hiromi Hirosaki University
Kasai, Shuya Hirosaki University
Harada, Nobuhiko Hirosaki University|Tohoku University
Kaufman, Randal J. Sanford Burnham Prebys Medical Discovery Research Institute
Itoh, Ken Hirosaki University
キーワード
Nrf2
ATF4
NGF
carnosic acid
antioxidant
資料タイプ
学術雑誌論文
抄録
Carnosic acid (CA) is a phytochemical found in some dietary herbs, such as Rosmarinus officinalis L., and possesses antioxidative and anti-microbial properties. We previously demonstrated that CA functions as an activator of nuclear factor, erythroid 2 (NF-E2)-related factor 2 (Nrf2), an oxidative stress-responsive transcription factor in human and rodent cells. CA enhances the expression of nerve growth factor (NGF) and antioxidant genes, such as HO-1 in an Nrf2-dependent manner in U373MG human astrocytoma cells. However, CA also induces NGF gene expression in an Nrf2-independent manner, since 50 μM of CA administration showed striking NGF gene induction compared with the classical Nrf2 inducer tert-butylhydroquinone (tBHQ) in U373MG cells. By comparative transcriptome analysis, we found that CA activates activating transcription factor 4 (ATF4) in addition to Nrf2 at high doses. CA activated ATF4 in phospho-eIF2α- and heme-regulated inhibitor kinase (HRI)-dependent manners, indicating that CA activates ATF4 through the integrated stress response (ISR) pathway. Furthermore, CA activated Nrf2 and ATF4 cooperatively enhanced the expression of NGF and many antioxidant genes while acting independently to certain client genes. Taken together, these results represent a novel mechanism of CA-mediated gene regulation evoked by Nrf2 and ATF4 cooperation.
掲載誌名
International Journal of Molecular Sciences
ISSN
14220067
16616596
cat書誌ID
AA12038549
出版者
MDPI
20
7
開始ページ
1706
発行日
2019-04-05
権利情報
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
先端酵素学研究所