Deciphering Molecular Basis for the Anti-Oxidative Stress Response and Application of the Basis for Disease Prevention and Therapy

• Project/Area Number: 19H05649
• Research Category: Grant-in-Aid for Scientific Research (S)
• Allocation Type: Single-year Grants
• Review Section: Broad Section H
• Research Institution: Tohoku University
• Principal Investigator: 山本 雅之 東北大学, 東北メディカル・メガバンク機構, 教授 (50166823)
• Co-Investigator(Kenkyū-buntansha): 田口 恵子 東北大学, 医学系研究科, 准教授 (20466527) ; 鈴木 隆史 東北大学, 医学系研究科, 准教授 (70508308)
• Project Period (FY): 2019-06-26 – 2024-03-31
• Project Status: Granted (Fiscal Year 2023)
• Budget Amount: ¥198,900,000 (Direct Cost: ¥153,000,000、Indirect Cost: ¥45,900,000); Fiscal Year 2023: ¥34,710,000 (Direct Cost: ¥26,700,000、Indirect Cost: ¥8,010,000); Fiscal Year 2022: ¥38,480,000 (Direct Cost: ¥29,600,000、Indirect Cost: ¥8,880,000); Fiscal Year 2021: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000); Fiscal Year 2020: ¥41,600,000 (Direct Cost: ¥32,000,000、Indirect Cost: ¥9,600,000); Fiscal Year 2019: ¥42,510,000 (Direct Cost: ¥32,700,000、Indirect Cost: ¥9,810,000)
• Keywords: ストレス応答 / Keap1

Outline of Research at the Start

私たちは常に外界からのストレスに曝されており、それに対する応答は生体の恒常性維持に必須である。酸素、紫外線、大気や食物中の化学物質など環境由来ストレスの増加は生体内レドックスバランスの撹乱を招来し、多くの疾患の共通基盤を形成している。健康長寿を実現するためには、生体の酸化ストレス応答機構全容の理解とその制御メカニズムの詳細な解明が極めて重要である。本研究では、生体の酸化ストレス応答機構において中心的な役割を果たしているKEAP1-NRF2制御系の機能メカニズムの解明に挑むとともに、ストレス関連疾患の予防・治療に対する同制御系の貢献を明らかにする。

Outline of Annual Research Achievements

私たちは常に外界からのストレスに曝されており、それに対する応答は生体の恒常性維持に必須である。酸素、紫外線、大気や食物中の化学物質などが重要な環境由来ストレスとなっているが、これらのストレス因子の増加は生体内レドックスバランスの撹乱を招来し、多くの疾患の共通基盤を形成している。超高齢化社会での健康長寿を実現するためには、生体の酸化ストレス応答機構全容の理解とその制御メカニズムの詳細な解明が極めて重要である。本研究では、生体の酸化 ストレス応答機構において中心的な役割を果たしているKEAP1-NRF2制御系の機能メカニズムの解明に挑むとともに、ストレス関連疾患の予防・治療に対する同制御系の貢献を明らかにする。特に、生体がKEAP1を利用して過剰な酸素によるストレスを感知するメカニズムとそのストレス感知が生体防御遺伝子群の発現の変化を惹起するメカニズムの解明に挑戦する。 当該年度は、放射線治療による口腔粘膜炎の保護にNRF2活性化が有効であることを明らかにした。本研究成果は、Free Radic Biol Med誌に報告した。 また、インスリン遺伝子変異による糖尿病モデルマウスAkitaを用いた解析により、NRF2欠失は糖尿病性腎疾患の増悪を引き起こすことを明らかにした。本研究成果は、Redox Biol誌に報告した。さらに、ハロフギノンを用いたNRF2阻害はNRF2活性化がんの治療に有効であることをマウスモデルを用いて実証した。本研究成果は、Free Radic Biol Med誌に報告した。この以上の成果は、NRF2活性に対する介入に基づく健康長寿戦略の有効性を示すものである。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

計画通り、遺伝子改変動物の解析および構造解析など順調に進んでいる。

Strategy for Future Research Activity

次年度は本プロジェクトの最終年度であり、これまでの成果の取りまとめおよび論文化を進める。特に、以下の点に注力する。
1.KEAP1-NRF2制御系による酸化ストレス感知メカニズムの解明。 KEAP1による酸化ストレスセンサーの機能解析について、含セレンタンパク質合成破綻マウスを用いて個体レベルの検証を実施し、その生理的重要性を実証する。
2. KEAP1-NRF2系の動的な構造・機能連関の解明。クライオ電子顕微鏡法およびX線結晶構造解析によるKEAP1-CUL3複合体の構造解析を行う。
3.NRF2活性に対する介入に基づく健康長寿戦略の確立と有効性検証。1)アルツハイマーモデルマウスにNRF2誘導剤を投与してその病態改善効果を調べる。すでに いくつかのNRF2誘導剤において有効な改善効果が確認されており、更なる検証を進める。 2)関節炎モデルマウスを用いてNRF2誘導剤投与あるいはKEAP1抑制によ りその病態改善効果を調べる。 3)IL6-LucマウスおよびKEAP1ノックダウン(NRF2活性化)IL6-Lucマウスを2024年に予定している国際宇宙ステーション滞在実験に向けて適合性試験などを行い、打ち上げマウスの準備を進める。

Assessment Rating

Interim Assessment Comments (Rating)

A: In light of the aim of introducing the research area into the research categories, the expected progress has been made in research.

Research Products

• [Int'l Joint Research] Fred Hutchinson Cancer Center(米国)
• [Int'l Joint Research] University of Dundee(英国)
• [Int'l Joint Research] Fred Hutchinson Cancer Center(米国)
• [Int'l Joint Research] University of Dundee(英国)
• [Int'l Joint Research] Fred Hutchinson Cancer Center(米国)
• [Int'l Joint Research] University of Dundee(英国)
• [Journal Article] Selective Elimination of NRF2-Activated Cells by Competition With Neighboring Cells in the Esophageal Epithelium (2023)
  • Author(s): Hirose Wataru、Horiuchi Makoto、Li Donghan、Motoike Ikuko N.、Zhang Lin、Nishi Hafumi、Taniyama Yusuke、Kamei Takashi、Suzuki Mikiko、Kinoshita Kengo、Katsuoka Fumiki、Taguchi Keiko、Yamamoto Masayuki
  • Journal Title: Cellular and Molecular Gastroenterology and Hepatology Volume: 15 Issue: 1 Pages: 153-178
  • DOI: 10.1016/j.jcmgh.2022.09.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] AHR and NRF2 in Skin Homeostasis and Atopic Dermatitis (2022)
  • Author(s): Edamitsu T, Taguchi K, Okuyama R, Yamamoto M
  • Journal Title: Antioxidants Volume: 11 Issue: 2 Pages: 227-227
  • DOI: 10.3390/antiox11020227
  • Peer Reviewed / Open Access
• [Journal Article] Multifaceted Roles of the KEAP1-NRF2 System in Cancer and Inflammatory Disease Milieu (2022)
  • Author(s): Panda Harit、Wen Huaichun、Suzuki Mikiko、Yamamoto Masayuki
  • Journal Title: Antioxidants Volume: 11 Issue: 3 Pages: 538-538
  • DOI: 10.3390/antiox11030538
  • Peer Reviewed / Open Access
• [Journal Article] Gene expression changes related to bone mineralization, blood pressure and lipid metabolism in mouse kidneys after space travel (2022)
  • Author(s): Suzuki Norio、Iwamura Yuma、Nakai Taku、Kato Koichiro、Otsuki Akihito、Uruno Akira、Saigusa Daisuke、Taguchi Keiko、Suzuki Mikiko、Shimizu Ritsuko、Yumoto Akane、Okada Risa、Shirakawa Masaki、Shiba Dai、Takahashi Satoru、Suzuki Takafumi、Yamamoto Masayuki
  • Journal Title: Kidney International Volume: 101 Issue: 1 Pages: 92-105
  • DOI: 10.1016/j.kint.2021.09.031
  • Peer Reviewed / Open Access
• [Journal Article] Esterification promotes the intracellular accumulation of roxadustat, an activator of hypoxia-inducible factors, to extend its effective duration. (2022)
  • Author(s): Nakai T, Saigusa D, Iwamura Y, Matsumoto Y, Umeda K, Kato K, Yamaki H, Tomioka Y, Hirano I, Koshiba S, Yamamoto M, Suzuki N*
  • Journal Title: Biochem Pharmacol Volume: 197 Pages: 114939-114939
  • DOI: 10.1016/j.bcp.2022.114939
  • Peer Reviewed / Open Access
• [Journal Article] Novel NRF2‐activated cancer treatments utilizing synthetic lethality (2022)
  • Author(s): Baird Liam、Kensler Thomas W.、Yamamoto Masayuki
  • Journal Title: IUBMB Life Volume: 74 Issue: 12 Pages: 1209-1231
  • DOI: 10.1002/iub.2680
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Halofuginone micelle nanoparticles eradicate Nrf2-activated lung adenocarcinoma without systemic toxicity (2022)
  • Author(s): Panda Harit、Suzuki Mikiko、Naito Mitsuru、Saito Ritsumi、Wen Huaichun、Baird Liam、Uruno Akira、Miyata Kanjiro、Yamamoto Masayuki
  • Journal Title: Free Radical Biology and Medicine Volume: 187 Pages: 92-104
  • DOI: 10.1016/j.freeradbiomed.2022.05.017
  • Peer Reviewed / Open Access
• [Journal Article] Nrf2 protects against radiation-induced oral mucositis via antioxidation and keratin layer thickening (2022)
  • Author(s): Wakamori Shun、Taguchi Keiko、Nakayama Yuki、Ohkoshi Akira、Sporn Michael B.、Ogawa Takenori、Katori Yukio、Yamamoto Masayuki
  • Journal Title: Free Radical Biology and Medicine Volume: 188 Pages: 206-220
  • DOI: 10.1016/j.freeradbiomed.2022.06.239
  • Peer Reviewed / Open Access
• [Journal Article] The β-TrCP-Mediated Pathway Cooperates with the Keap1-Mediated Pathway in Nrf2 Degradation <i>In Vivo</i> (2022)
  • Author(s): Kuga Ayumi、Tsuchida Kouhei、Panda Harit、Horiuchi Makoto、Otsuki Akihito、Taguchi Keiko、Katsuoka Fumiki、Suzuki Mikiko、Yamamoto Masayuki
  • Journal Title: Molecular and Cellular Biology Volume: 42 Issue: 7 Pages: 1-22
  • DOI: 10.1128/mcb.00563-21
  • Peer Reviewed / Open Access
• [Journal Article] Target Gene Diversity of the Nrf1-MafG Transcription Factor Revealed by a Tethered Heterodimer (2022)
  • Author(s): Katsuoka Fumiki、Otsuki Akihito、Hatanaka Nozomi、Okuyama Haruna、Yamamoto Masayuki
  • Journal Title: Molecular and Cellular Biology Volume: 42 Issue: 3
  • DOI: 10.1128/mcb.00520-21
  • Peer Reviewed / Open Access
• [Journal Article] Nrf2 deficiency deteriorates diabetic kidney disease in Akita model mice (2022)
  • Author(s): Liu Yexin、Uruno Akira、Saito Ritsumi、Matsukawa Naomi、Hishinuma Eiji、Saigusa Daisuke、Liu Hong、Yamamoto Masayuki
  • Journal Title: Redox Biology Volume: 58 Pages: 102525-102525
  • DOI: 10.1016/j.redox.2022.102525
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The KEAP1-NRF2 system and esophageal cancer (2022)
  • Author(s): Hirose W, Oshikiri H, Taguchi K, Yamamoto M
  • Journal Title: Cancers Volume: 14 Issue: 19 Pages: 4702-4702
  • DOI: 10.3390/cancers14194702
  • Peer Reviewed / Open Access
• [Journal Article] The isoquinoline PRL-295 increases the thermostability of Keap1 and disrupts its interaction with Nrf2 (2022)
  • Author(s): Dayalan Naidu S、Suzuki T、Dikovskaya D、Knatko EV、Higgins M、Sato M、Novak M、Villegas JA、Moore TW、Yamamoto M、Dinkova-Kostova AT.
  • Journal Title: iScience Volume: 25 Issue: 1 Pages: 103703-103703
  • DOI: 10.1016/j.isci.2021.103703
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Distinct Regulations of HO-1 Gene Expression for Stress Response and Substrate Induction (2021)
  • Author(s): Zhang Anqi、Suzuki Takafumi、Adachi Saki、Naganuma Eriko、Suzuki Norio、Hosoya Tomonori、Itoh Ken、Sporn Michael B.、Yamamoto Masayuki
  • Journal Title: Molecular and Cellular Biology Volume: 41 Issue: 11 Pages: 0023621-0023621
  • DOI: 10.1128/mcb.00236-21
  • Peer Reviewed / Open Access
• [Journal Article] Nrf2 plays a critical role in the metabolic response during and after spaceflight (2021)
  • Author(s): Uruno A、Saigusa D、Suzuki T、Yumoto A、Nakamura T、Matsukawa N、Yamazaki T、Saito R、Taguchi K、Suzuki M、Suzuki N、Otsuki A、Katsuoka F、Hishinuma E、Okada R、Koshiba S、Tomioka Y、Shimizu R、Shirakawa M、Kensler TW.、Shiba D、Yamamoto M
  • Journal Title: Communications Biology Volume: 4 Issue: 1 Pages: 1381-1381
  • DOI: 10.1038/s42003-021-02904-6
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Novel method for evaluating the health condition of mice in space through a video downlink (2021)
  • Author(s): YUMOTO Akane、KOKUBO Toshiaki、IZUMI Ryutaro、SHIMOMURA Michihiko、FUNATSU Osamu、TADA Motoki N.、OTA-MURAKAMI Naoko、IINO Kayoko、SHIRAKAWA Masaki、MIZUNO Hiroyasu、KUDO Takashi、TAKAHASHI Satoru、SUZUKI Takafumi、URUNO Akira、YAMAMOTO Masayuki、SHIBA Dai
  • Journal Title: Experimental Animals Volume: 70 Issue: 2 Pages: 236-244
  • DOI: 10.1538/expanim.20-0102
  • NAID: 130008037417
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed
• [Journal Article] The Transcription Factor MAFF Regulates an Atherosclerosis Relevant Network Connecting Inflammation and Cholesterol Metabolism (2021)
  • Author(s): von Scheidt Moritz、Zhao Yuqi、de Aguiar Vallim Thomas Q.、Che Nam、Wierer Michael、Seldin Marcus M.、Franzen Oscar、Kurt Zeyneb、Pang Shichao、Bongiovanni Dario、Yamamoto Masayuki、Edwards Peter A.、Ruusalepp Arno、Kovacic Jason C.、Mann Matthias、Bjorkegren Johan L.M.、Lusis Aldons J.、Yang Xia、Schunkert Heribert
  • Journal Title: Circulation Volume: - Issue: 18 Pages: 1809-1823
  • DOI: 10.1161/circulationaha.120.050186
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nrf2 Activation Sensitizes K-Ras Mutant Pancreatic Cancer Cells to Glutaminase Inhibition (2021)
  • Author(s): Hamada S, Matsumoto R, Tanaka Y, Taguchi K, Yamamoto M, Masamune A.
  • Journal Title: Int J Mol Sci. Volume: 22 Issue: 4 Pages: 1870-1870
  • DOI: 10.3390/ijms22041870
  • Peer Reviewed / Open Access
• [Journal Article] CL316243 treatment mitigates the inflammation in white adipose tissues of juvenile adipocyte-specific Nfe2l1 knockout mice (2021)
  • Author(s): Wang Zhendi、Hou Yongyong、Ren Suping、Liu Zhiyuan、Zuo Zhuo、Huang Sicui、Wang Wanqi、Wang Huihui、Chen Yanyan、Xu Yuanyuan、Yamamoto Masayuki、Zhang Qiang、Fu Jingqi、Pi Jingbo
  • Journal Title: Free Radical Biology and Medicine Volume: 165 Pages: 289-298
  • DOI: 10.1016/j.freeradbiomed.2021.01.043
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The KEAP1-NRF2 system as a molecular target of cancer treatment (2021)
  • Author(s): Taguchi K, Yamamoto M
  • Journal Title: Cancers Volume: 13 Issue: 1 Pages: 46-46
  • DOI: 10.3390/cancers13010046
  • Peer Reviewed / Open Access
• [Journal Article] Nrf2 is activated by disruption of mitochondrial thiol homeostasis but not by enhanced mitochondrial superoxide production (2021)
  • Author(s): Cvetko Filip、Caldwell Stuart T.、Higgins Maureen、Suzuki Takafumi、Yamamoto Masayuki、Prag Hiran A.、Hartley Richard C.、Dinkova-Kostova Albena T.、Murphy Michael P.
  • Journal Title: Journal of Biological Chemistry Volume: 296 Pages: 100169-100169
  • DOI: 10.1074/jbc.ra120.016551
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Identification of Dominant Transcripts in Oxidative Stress Response by a Full-Length Transcriptome Analysis (2020)
  • Author(s): Otsuki Akihito、Okamura Yasunobu、Aoki Yuichi、Ishida Noriko、Kumada Kazuki、Minegishi Naoko、Katsuoka Fumiki、Kinoshita Kengo、Yamamoto Masayuki
  • Journal Title: Molecular and Cellular Biology Volume: 41 Issue: 2 Pages: 1-18
  • DOI: 10.1128/mcb.00472-20
  • Peer Reviewed / Open Access
• [Journal Article] Cellular Nrf2 levels determine cell fate during chemical carcinogenesis in esophageal epithelium (2020)
  • Author(s): Horiuchi M, Taguchi K, Hirose W, Tsuchida K, Suzuki M, Taniyama Y, Kamei T, Yamamoto M.
  • Journal Title: Mol Cell Biol Volume: 41 Issue: 2
  • DOI: 10.1128/mcb.00536-20
  • Peer Reviewed
• [Journal Article] NRF2-Dependent Bioactivation of Mitomycin C as a Novel Strategy To Target KEAP1-NRF2 Pathway Activation in Human Cancer (2020)
  • Author(s): Baird Liam、Yamamoto Masayuki
  • Journal Title: Molecular and Cellular Biology Volume: 41 Issue: 2 Pages: 1-18
  • DOI: 10.1128/mcb.00473-20
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Environmental pollutants and the immune response (2020)
  • Author(s): Suzuki Takafumi、Hidaka Takanori、Kumagai Yoshito、Yamamoto Masayuki
  • Journal Title: Nature Immunology Volume: 21 Issue: 12 Pages: 1486-1495
  • DOI: 10.1038/s41590-020-0802-6
  • NAID: 40022683384
  • Peer Reviewed / Open Access
• [Journal Article] The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway (2020)
  • Author(s): Baird Liam、Yamamoto Masayuki
  • Journal Title: Molecular and Cellular Biology Volume: 40 Issue: 13 Pages: 1-23
  • DOI: 10.1128/mcb.00099-20
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Microenvironmental activation of Nrf2 restricts the progression of Nrf2-activated malignant tumors (2020)
  • Author(s): Makiko Hayashi, Ayumi Kuga, Mikiko Suzuki, Harit Panda, Hiroshi Kitamura, Hozumi Motohashi, Masayuki Yamamoto
  • Journal Title: Cancer Research Volume: 0 Issue: 16 Pages: 00-00
  • DOI: 10.1158/0008-5472.can-19-2888
  • Peer Reviewed
• [Journal Article] Geldanamycin-Derived HSP90 Inhibitors Are Synthetic Lethal with NRF2 (2020)
  • Author(s): Baird Liam、Suzuki Takafumi、Takahashi Yushi、Hishinuma Eiji、Saigusa Daisuke、Yamamoto Masayuki
  • Journal Title: Molecular and Cellular Biology Volume: 40 Issue: 22 Pages: 1-22
  • DOI: 10.1128/mcb.00377-20
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nrf2 contributes to the weight gain of mice during space travel (2020)
  • Author(s): Suzuki, T., et al., Koshiba, S. et al., Yamamoto, M.（合計37名、本研究者は18番目）
  • Journal Title: Communications Biology Volume: 3 Issue: 1 Pages: 496-496
  • DOI: 10.1038/s42003-020-01227-2
  • NAID: 120007161347
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Impacts of NRF2 activation in non?small‐cell lung cancer cell lines on extracellular metabolites (2020)
  • Author(s): Saigusa Daisuke、Motoike Ikuko N.、Saito Sakae、Zorzi Michael、Aoki Yuichi、Kitamura Hiroshi、Suzuki Mikiko、Katsuoka Fumiki、Ishii Hirofumi、Kinoshita Kengo、Motohashi Hozumi、Yamamoto Masayuki
  • Journal Title: Cancer Science Volume: 111 Issue: 2 Pages: 667-678
  • DOI: 10.1111/cas.14278
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration (2020)
  • Author(s): Afshinnekoo Ebrahim、Scott Ryan T.、MacKay Matthew J.、Pariset Eloise、Cekanaviciute Egle、Barker Richard、Gilroy Simon、Hassane Duane、Smith Scott M.、Zwart Sara R.、Nelman-Gonzalez Mayra、Crucian Brian E.、Ponomarev Sergey A.、Orlov Oleg I.、Shiba Dai、Muratani Masafumi、Yamamoto Masayuki、以降著者省略
  • Journal Title: Cell Volume: 183 Issue: 5 Pages: 1162-1184
  • DOI: 10.1016/j.cell.2020.10.050
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Enhancer remodeling promotes tumor-initiating activity in NRF2-activated non-small cell lung cancers (2020)
  • Author(s): Okazaki Keito、Anzawa Hayato、Liu Zun、Ota Nao、Kitamura Hiroshi、Onodera Yoshiaki、Alam Md. Morshedul、Matsumaru Daisuke、et al.
  • Journal Title: Nature Communications Volume: 11 Issue: 1 Pages: 5911-5911
  • DOI: 10.1038/s41467-020-19593-0
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Possible Roles of Proinflammatory Signaling in Keratinocytes Through Aryl Hydrocarbon Receptor Ligands for the Development of Squamous Cell Carcinoma (2020)
  • Author(s): Sato Yota、Fujimura Taku、Hidaka Takanori、Lyu Chunbing、Tanita Kayo、Matsushita Shigeto、Yamamoto Masayuki、Aiba Setsuya
  • Journal Title: Frontiers in Immunology Volume: 11 Pages: 534323-534323
  • DOI: 10.3389/fimmu.2020.534323
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Preconditioning the immature lung with enhanced Nrf2 activity protects against oxidant-induced hypoalveolarization in mice (2020)
  • Author(s): Tamatam Chandra M.、Reddy Narsa M.、Potteti Haranatha R.、Ankireddy Aparna、Noone Patrick M.、Yamamoto Masayuki、Kensler Thomas W.、Reddy Sekhar P.
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 19034-19034
  • DOI: 10.1038/s41598-020-75834-8
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Protracted rosiglitazone treatment exacerbates inflammation in white adipose tissues of adipocyte-specific Nfe2l1 knockout mice (2020)
  • Author(s): Ren Suping、Hou Yongyong、Zuo Zhuo、Liu Zhiyuan、Wang Huihui、Xu Yuanyuan、Yamamoto Masayuki、Zhang Qiang、Fu Jingqi、Pi Jingbo
  • Journal Title: Food and Chemical Toxicology Volume: 146 Pages: 111836-111836
  • DOI: 10.1016/j.fct.2020.111836
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Nrf2 Lowers the Risk of Lung Injury via Modulating the Airway Innate Immune Response Induced by Diesel Exhaust in Mice (2020)
  • Author(s): Li YJ, Shimizu T, Shinkai Y, Ihara T, Sugamata T, Kato K, Kobayashi M, Hirata Y, Inagaki H, Uzuki M, Akimoto T, Umezawa M, Takeda K, Azuma A, Yamamoto M, Kawada T.
  • Journal Title: Biomedicines Volume: 8 Issue: 10 Pages: 443-443
  • DOI: 10.3390/biomedicines8100443
  • Peer Reviewed / Open Access
• [Journal Article] Effects of post-renal anemia treatment with the HIF-PHD inhibitor molidustat on adenine-induced renal anemia and kidney disease in mice (2020)
  • Author(s): Li Lei、Nakano Daisuke、Zhang Anqi、Kittikulsuth Wararat、Morisawa Norihiko、Ohsaki Hiroyuki、Suzuki Norio、Yamamoto Masayuki、Nishiyama Akira
  • Journal Title: Journal of Pharmacological Sciences Volume: 144 Issue: 4 Pages: 229-236
  • DOI: 10.1016/j.jphs.2020.09.004
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association of single nucleotide polymorphisms in the NRF2 promoter with vascular stiffness with aging (2020)
  • Author(s): Shimizu Sunao、Mimura Junsei、Hasegawa Takanori、Shimizu Eigo、Imoto Seiya、Tsushima Michiko、Kasai Shuya、Yamazaki Hiromi、Ushida Yusuke、Suganuma Hiroyuki、Tomita Hirofumi、Yamamoto Masayuki、Nakaji Shigeyuki、Itoh Ken
  • Journal Title: PLOS ONE Volume: 15 Issue: 8 Pages: e0236834-e0236834
  • DOI: 10.1371/journal.pone.0236834
  • Peer Reviewed
• [Journal Article] Nrf2 Antioxidative System is Involved in Cytochrome P450 Gene Expression and Activity: A Delay in Pentobarbital Metabolism in Nrf2-Deficient Mice (2020)
  • Author(s): Ashino Takashi、Yamamoto Masayuki、Numazawa Satoshi
  • Journal Title: Drug Metabolism and Disposition Volume: 48 Issue: 8 Pages: 673-680
  • DOI: 10.1124/dmd.120.000010
  • Peer Reviewed
• [Journal Article] Inhibitors of the protein-protein interaction between phosphorylated p62 and Keap1 attenuate chemoresistance in a human hepatocellular carcinoma cell line (2020)
  • Author(s): Daisuke Yasuda, Tomoyuki Ohe, Kyoko Takahashi, Riyo Imamura, Hirotatsu Kojima, Takayoshi Okabe, Yoshinobu Ichimura, Masaaki Komatsu, Masayuki Yamamoto, Tetsuo Nagano, Tadahiko Mashino
  • Journal Title: Free Radical Research Volume: Mar 30 Issue: 11-12 Pages: 1-13
  • DOI: 10.1080/10715762.2020.1732955
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Keap1 deletion accelerates mutant K-ras/p53-driven cholangiocarcinoma (2020)
  • Author(s): 1.Nabeshima T, Hamada S, Taguchi K, Tanaka Y, Matsumoto R, Yamamoto M, Masamune A
  • Journal Title: Am J Physiol Gastrointest Liver Physiol Volume: 318 Issue: 3 Pages: G419-G427
  • DOI: 10.1152/ajpgi.00296.2019
  • Peer Reviewed
• [Journal Article] Nrf2 Suppresses Oxidative Stress and Inflammation in App Knock-in Alzheimer’s Disease Model Mice. (2020)
  • Author(s): 3)(*Equal contribution) Uruno A*, Matsumaru D*, Ryoke R, Saito R, Kadoguchi S, Saigusa D, Saito T, Saido TC, Kawashima R, Yamamoto M.
  • Journal Title: Mol Cell Biol. Volume: 40 Issue: 6
  • DOI: 10.1128/mcb.00467-19
  • Peer Reviewed
• [Journal Article] Molecular Mechanism of Cellular Oxidative Stress Sensing by Keap1 (2019)
  • Author(s): Suzuki Takafumi、Muramatsu Aki、Saito Ryota、Iso Tatsuro、Shibata Takahiro、Kuwata Keiko、Kawaguchi Shin-ichi、Iwawaki Takao、Adachi Saki、Suda Hiromi、Morita Masanobu、Uchida Koji、Baird Liam、Yamamoto Masayuki
  • Journal Title: Cell Reports Volume: 28 Issue: 3 Pages: 746-758
  • DOI: 10.1016/j.celrep.2019.06.047
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Bardoxolone methyl analog attenuates proteinuria-induced tubular damage by modulating mitochondrial function (2019)
  • Author(s): Nagasu Hajime、Sogawa Yuji、Kidokoro Kengo、Itano Seiji、Yamamoto Toshiya、Satoh Minoru、Sasaki Tamaki、Suzuki Takafumi、Yamamoto Masayuki、Wigley W. Christian、Proksch Joel W.、Meyer Colin J.、Kashihara Naoki
  • Journal Title: The FASEB Journal Volume: 33 Issue: 11 Pages: 12253-12263
  • DOI: 10.1096/fj.201900217r
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of Nrf2 in inflammatory response in lung of mice exposed to zinc oxide nanoparticles (2019)
  • Author(s): Sehsah Radwa、Wu Wenting、Ichihara Sahoko、Hashimoto Naozumi、Hasegawa Yoshinori、Zong Cai、Itoh Ken、Yamamoto Masayuki、Elsayed Ahmed Ali、El-Bestar Soheir、Kamel Emily、Ichihara Gaku
  • Journal Title: Particle and Fibre Toxicology Volume: 16 Issue: 1 Pages: 47-47
  • DOI: 10.1186/s12989-019-0328-y
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dietary supplementation with sulforaphane attenuates liver damage and heme overload in a sickle cell disease murine model (2019)
  • Author(s): Panda Harit、Keleku-Lukwete Nadine、Kuga Ayumi、Fuke Nobuo、Suganuma Hiroyuki、Suzuki Mikiko、Yamamoto Masayuki
  • Journal Title: Experimental Hematology Volume: 77 Pages: 51-60.e1
  • DOI: 10.1016/j.exphem.2019.08.001
  • Peer Reviewed
• [Journal Article] Direct and Specific Functional Evaluation of the Nrf2 and MafG Heterodimer by Introducing a Tethered Dimer into Small Maf-Deficient Cells (2019)
  • Author(s): Katsuoka Fumiki、Otsuki Akihito、Takahashi Mizue、Ito Shin、Yamamoto Masayuki
  • Journal Title: Molecular and Cellular Biology Volume: 39 Issue: 20
  • DOI: 10.1128/mcb.00273-19
  • Peer Reviewed / Open Access
• [Presentation] The KEAP1-NRF2 System in Biology and Medicine (2022)
  • Author(s): Yamamoto M
  • Organizer: Cancer Seminar for Honorary Doctorate at University of Eastern Finland
  • Int'l Joint Research / Invited
• [Presentation] The KEAP1-NRF2 pathway regulating cellular response against oxidative and electrophilic stresses (2022)
  • Author(s): Yamamoto M
  • Organizer: Kunio Yagi Lecture on IUBMB-FEBS Congress,
  • Int'l Joint Research / Invited
• [Presentation] Regulation of NRF2-KEAP1 Stress Sensing Mechanisms in the Kidney (2022)
  • Author(s): Yamamoto M
  • Organizer: Keynote Lecture at the FASEB Science Research Conferences on Polycystic Kidney Disease: Hurdles and Advancesin Molecular Mechanisms and Therapies
  • Int'l Joint Research / Invited
• [Presentation] Elucidation of molecular basis of oxidative stress response utilizing mouse, human and space biology (2022)
  • Author(s): Yamamoto M
  • Organizer: Redox Week in Sendai 2022
  • Int'l Joint Research / Invited
• [Presentation] The KEAP1-NRF2 System in Cancer Biology and Medicine (2022)
  • Author(s): Yamamoto M
  • Organizer: The 53rd Korean Academy of Science and Technology (KAST) International Symposium
  • Int'l Joint Research / Invited
• [Presentation] Molecular Basis of Oxidative Stress Sensing and Diseases (2022)
  • Author(s): Yamamoto M
  • Organizer: The 10th Biennial Meeting of Society for Free Radical Research-Asia: New Paradigm for Research on Oxidative Stress & Inflammation.
  • Int'l Joint Research / Invited
• [Presentation] Keap1-Nrf2 Antioxidative stress response system (2019)
  • Author(s): Yamamoto M
  • Organizer: Paris Redox 2019,
  • Int'l Joint Research / Invited
• [Presentation] 酸化ストレス応答の分子メカニズムと病態 (2019)
  • Author(s): 山本雅之
  • Organizer: CVMW2019心血管代謝週間
  • Invited
• [Presentation] 宇宙ストレスにおける環境応答型転写因子Nrf2の役割 (2019)
  • Author(s): 山本雅之
  • Organizer: JAXA 小動物飼育ミッション 宇宙実験 知見交換会
  • Invited
• [Presentation] KEAP1-NRF2 制御系と発がん (2019)
  • Author(s): 山本雅之
  • Organizer: 第7回がんと代謝研究会
  • Invited
• [Presentation] KEAP1センサー機能の分子基盤の解明 (2019)
  • Author(s): 山本雅之
  • Organizer: 第92回日本生化学会大会
  • Invited
• [Remarks] 東北大学大学院医学系研究科医化学分野
  • URL: http://www.dmbc.med.tohoku.ac.jp/official/index.html
• [Funded Workshop] The Environmental Response V, 17th JBS Biofrontier Symposium (2019)