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Mechanism of Rapid Nuclear Factor-E2-Related Factor 2 (Nrf2) Activation via Membrane-Associated Estrogen Receptors: Roles of NADPH Oxidase 1, Neutral Sphingomyelinase 2 and Epidermal Growth Factor Receptor (EGFR)
http://hdl.handle.net/2241/00160232
http://hdl.handle.net/2241/0016023298ef4a13-facd-41cd-b0ed-7c6d94a6f550
名前 / ファイル | ライセンス | アクション |
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ANT_8-3 (656.2 kB)
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Item type | Journal Article(1) | |||||
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公開日 | 2020-06-26 | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Mechanism of Rapid Nuclear Factor-E2-Related Factor 2 (Nrf2) Activation via Membrane-Associated Estrogen Receptors: Roles of NADPH Oxidase 1, Neutral Sphingomyelinase 2 and Epidermal Growth Factor Receptor (EGFR) | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
蕨, 栄治
× 蕨, 栄治× Ishii, Tetsuro |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Membrane-associated estrogen receptors (ER)-α36 and G protein-coupled estrogen receptor (GPER) play important roles in the estrogen’s rapid non-genomic actions including stimulation of cell proliferation. Estrogen via these receptors induces rapid activation of transcription factor nuclear factor-E2-related factor 2 (Nrf2), a master regulator of detoxification and antioxidant systems, playing a key role in the metabolic reprogramming to support cell proliferation. This review highlights the possible mechanism underlying rapid Nrf2 activation via membrane-associated estrogen receptors by estrogen and phytoestrogens. Stimulation of ER-α36-GPER signaling complex rapidly induces Src-mediated transactivation of epidermal growth factor receptor (EGFR) leading to a kinase-mediated signaling cascade. We propose a novel hypothesis that ER-α36-GPER signaling initially induces rapid and temporal activation of NADPH oxidase 1 to generate superoxide, which subsequently activates redox-sensitive neutral sphingomyelinase 2 generating the lipid signaling mediator ceramide. Generation of ceramide is required for Ras activation and ceramide-protein kinase C ζ-casein kinase 2 (CK2) signaling. Notably, CK2 enhances chaperone activity of the Cdc37-Hsp90 complex supporting activation of various signaling kinases including Src, Raf and Akt (protein kinase B). Activation of Nrf2 may be induced by cooperation of two signaling pathways, (i) Nrf2 stabilization by direct phosphorylation by CK2 and (ii) EGFR-Ras-PI 3 kinase (PI3K)-Akt axis which inhibits glycogen synthase kinase 3β leading to enhanced nuclear transport and stability of Nrf2. | |||||
書誌情報 |
en : Antioxidants 巻 8, 号 3, p. 69, 発行日 2019-03 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2076-3921 | |||||
PubMed番号 | ||||||
識別子タイプ | PMID | |||||
関連識別子 | 30889865 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | 10.3390/antiox8030069 | |||||
権利 | ||||||
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/). | |||||
著者版フラグ | ||||||
値 | publisher | |||||
出版者 | ||||||
出版者 | MDPI |