Transcriptional regulation by reactive oxygen species

2012 Fiscal Year Final Research Report

• Project Area: Signaling functions of reactive oxygen species
• Project/Area Number: 20117010
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hirosaki University
• Principal Investigator: ITOH Ken 弘前大学, 医学(系)研究科(研究院), 教授 (10323289)
• Co-Investigator(Kenkyū-buntansha): SATOH Takumi 岩手大学, 工学部, 准教授 (10300831)
• Co-Investigator(Renkei-kenkyūsha): MIMURA Junsei 弘前大学, 医学(系)研究科(研究院), 講師 (60344884) ; MARUYAMA Atsushi 弘前大学, 医学(系)研究科(研究院), 助教 (10431438)
• Project Period (FY): 2008 – 2012
• Keywords: 活性酸素 / Nrf2 / ストレス応答

Research Abstract

To clarify the transcription regulation in response to reactive oxygen species and its roles in pathophysiology, we analyzed it focusing on Nrf2. We identified KAP1, GCN1L1 and ATF4 as novel Nrf2-interacting proteins and showed that they cooperate with Nrf2 for the protection against oxidative stress. Furthermore, we have clarified that Nrf2 promotes atherosclerosis formation in the advanced stage of high fat diet-induced atherosclerosis model in mice.

Research Products

• [Journal Article] Nrf2 activation is associated with Z-DNA formation in the human HO-1 promoter (2013)
  • Author(s): Maruyama A, Mimura J, Harada N, Itoh K
  • Journal Title: Nucleic Acids Res Volume: (in press)
  • DOI: doi:10.1093/nar/gkt243
  • Peer Reviewed
• [Journal Article] Carnosic acid suppresses the production of amyloid-β 1-42 by inducing the metalloprotease gene TACE/ADAM17 in SH-SY5Y human neuroblastoma cells (2013)
  • Author(s): Meng P, Yoshida H, Matsumiya T, Imaizumi T, Tanji K, Xing F, Hayakari R, Dempoya J, Tatsuta T, Aizawa-Yashiro T, Mimura J, Kosaka K, Itoh K, Satoh K
  • Journal Title: Neurosci Res Volume: 75 Pages: 4-102
  • DOI: doi:10.1016/j.neures.2012.11.007
  • Peer Reviewed
• [Journal Article] Keap1 is localized in neuronal and glial cytoplasmic inclusions in various neurodegenerative diseases (2013)
  • Author(s): Tanji K, Maruyama A, Odagiri S, Mori F, Itoh K, Kakita A, Takahashi H, Wakabayashi K
  • Journal Title: J Neuropathol Exp Neurol Volume: 72 Pages: 18-28
  • DOI: doi: 10.1097/NEN.0b013e31827b5713
  • Peer Reviewed
• [Journal Article] Nrf2 in bone marrow-derived cells positively contributes to the advanced stage of atherosclerotic plaque formation (2012)
  • Author(s): Harada N, Ito K, Hosoya T, Mimura J, Maruyama A, Noguchi N, Yagami KI, Morito N, Takahashi S, Maher JM, Yamamoto M, Itoh K
  • Journal Title: Free Radic Biol Med Volume: 53 Pages: 2256-2262
  • DOI: doi:10.1016/j.freeradbiomed.2012.10.001
  • Peer Reviewed
• [Journal Article] Nrf2 inhibits hepatic iron accumulation and counteracts oxidative stress-induced liver injury in nutritional steatohepatitis (2012)
  • Author(s): Okada K, Warabi E, Sugimoto H, Horie M, Tokushige K, Ueda T, Harada N, Taguchi K, Hashimoto E, Itoh K, Ishii T, Utsunomiya H, Yamamoto M, Shoda J
  • Journal Title: J Gastroenterol Volume: 47 Pages: 924-935
  • DOI: doi:10.1007/s00535-012-0552-9
  • Peer Reviewed
• [Journal Article] Methylation of the KEAP1 gene promoter region in human colorectal cancer (2012)
  • Author(s): Hanada N, Takahata T, Zhou Q, Ye X, Sun R, Itoh J, Ishiguro A, Kijima H, Mimura J, Itoh K, Fukuda S, Saijo Y
  • Journal Title: BMC Cancer Volume: 12 Pages: 66
  • DOI: doi:10.1186/1471-2407-12-66
  • Peer Reviewed
• [Journal Article] Molecular mechanisms for the regulation of Nrf2-mediated cell proliferation in non-small-cell lung cancers (2012)
  • Author(s): Yamadori T, Ishii Y, Homma S, Morishima Y, Kurishima K, Itoh K, Yamamoto M, Minami Y, Noguchi M, Hizawa N
  • Journal Title: Oncogene Volume: 31 Pages: 4768-4777
  • DOI: doi:10.1038/onc.2011.628
  • Peer Reviewed
• [Journal Article] Syinpilin 1-binding protein NUB1 is colocalized with nonfibrillar, proteinase K-resistant・-synuclein in presynapses in Lewy Body disease (2011)
  • Author(s): Tanji K, Mori F, Kito K, Kakita A, Mimura J, Itoh K, Takahashi H, Kamitani T, Wakabayashi K
  • Journal Title: J Neuropathol Exp Neurol Volume: 70 Pages: 879-889
  • DOI: doi:10.1097/NEN.0b013e3182303745
  • Peer Reviewed
• [Journal Article] Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes (2011)
  • Author(s): Mimura J, Kosaka K, Maruyama A, Satoh T, Harada N, Yoshida H, Satoh K, Yamamoto M, Itoh K
  • Journal Title: J Biochem Volume: 50 Pages: 209-217
  • DOI: doi:10.1093/jb/mvr065
  • Peer Reviewed
• [Journal Article] Nrf2 degron-fused reporter system: a new tool for specific evaluation of Nrf2 inducers (2011)
  • Author(s): Hirotsu Y, Katsuoka F, Itoh K, Yamamoto M
  • Journal Title: Genes Cells Volume: 16 Pages: 406-415
  • DOI: doi:10.1111/j.1365-2443.2011.01496.x
  • Peer Reviewed
• [Journal Article] The Novel Nrf2-interacting factor KAP1 regulates susceptibility to oxidaive stress by promoting the Nrf2-mediated cytoprotective response (2011)
  • Author(s): Maruyama A, Nishikawa K, Kawatani Y, Mimura J, Hosoya T, Harada N, Yamamato M and Itoh K
  • Journal Title: Biochemical J Volume: 436 Pages: 387-397
  • DOI: doi:10.1042/BJ20101748
  • Peer Reviewed
• [Journal Article] Role of Nrf2 in Host Defense against Influenza in Cigarette Smoke-Exposed Mice (2011)
  • Author(s): Yageta Y, Ishii Y, Morishima Y, Masuko H, Ano S, Yamadori T, Itoh K, Takeuchi K, Yamamoto M, Hizawa N
  • Journal Title: J Virology Volume: 85 Pages: 4679-4690
  • DOI: doi:10.1128/JVI.02456-10
  • Peer Reviewed
• [Journal Article] Nrf2 regulates ferroportin 1-mediated iron efflux and counteracts lipopolysaccharide-induced ferroportin 1 mRNA suppression in macrophages (2011)
  • Author(s): Harada N, Kanayama M, Maruyama A, Yoshida A, Tazumi K, Hosoya T, Mimura J, Toki T, Maher JM, Yamamoto M, Itoh K
  • Journal Title: Arch Biochem Biophys Volume: 508 Pages: 101-109
  • DOI: doi:10.1016/j.abb.2011.02.001
  • Peer Reviewed
• [Journal Article] Edaravone and carnosic acid synergistically enhance the expression of nerve growth factor in human astrocytes under hypoxia/reoxygenation (2011)
  • Author(s): Yoshida H, Mimura J, Imaizumi T, Matsumiya T, Ishikawa A, Metoki N, Tanji K, Ota K, Hayakari R, Kosaka K, Itoh K, Satoh K
  • Journal Title: Neurosci Res Volume: 69 Pages: 291-298
  • DOI: doi:10.1016/j.neures.2010.12.016
  • Peer Reviewed
• [Journal Article] p122 protein enhances intracellular calcium increase to acetylcholine: its possible role in the pathogenesis of coronary spastic angina (2010)
  • Author(s): Murakami R, Osanai T, Tomita H, Sasaki S, Maruyama A, Itoh K, Homma Y, Okumura K
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 30 Pages: 1968-1975
  • DOI: doi:10.1161/ATVBAHA.110.203083
  • Peer Reviewed
• [Journal Article] Aggressive mammary carcinoma progression in Nrf2 knockout mice treated with 7,12-dimethylbenz[a]anthracene (2010)
  • Author(s): Becks L, Prince M, Burson H, Christophe C, Broadway M, Itoh K, Yamamoto M, Mathis M, Orchard E, Shi R, McLarty J, Pruitt K, Zhang S, Kleiner-Hancock HE
  • Journal Title: BMC Cancer Volume: 10 Pages: 540
  • DOI: doi:10.1186/1471-2407-10-540
  • Peer Reviewed
• [Journal Article] Relationship between radiosensitivity and Nrf2 target gene expression in human hematopoieic stem cells (2010)
  • Author(s): Kato K, Takahashi K, Monzen S, Yamamoto H, Mruyama A, Itoh K, Kashiwakura I
  • Journal Title: Radiat Res Volume: 174 Pages: 177-184
  • DOI: doi:10.1667/RR2146.1
  • Peer Reviewed
• [Journal Article] Suppression of SLC11A2 Expression Is Essential to Maintain Duodenal Integrity During Dietary Iron Overload (2010)
  • Author(s): Shirase T, Mori K, Okazaki Y, Itoh K, Yamamoto M, Tabuchi M, Kishi F, Jiang L, Akatsuka S, Nakao K, Toyokuni S
  • Journal Title: Am J Pathol Volume: 177 Pages: 677-685
  • DOI: doi:10.2353/ajpath.2010.090823
  • Peer Reviewed
• [Journal Article] Ablation of the Transcription Factor Nrf2 Promotes Ischemia-Induced Neovascularization by Enhancing the Inflammatory Response (2010)
  • Author(s): Ichihara S, Yamada Y, Liu F, Murohara T, Itoh K, Yamamoto M, Ichihara G
  • Journal Title: Arterioscler Thromb Vasc Biol Volume: 30 Pages: 1553-1561
  • DOI: doi: 10.1161/ATVBAHA.110.204123
  • Peer Reviewed
• [Journal Article] Discovery of the negative regulator of Nrf2, Keap1: A historical overview (2010)
  • Author(s): Itoh K, Mimura J, Yamamoto M
  • Journal Title: Antioxid Redox Signal Volume: 120 Pages: 145-154
  • DOI: doi:10.1089/ars.2010.3222
  • Peer Reviewed
• [Journal Article] Increased susceptibility of Nrf2 null mice to 1-bromopropane-induced hepatotoxicity (2010)
  • Author(s): Liu F, Ichihara S, Valentine WM, Itoh K, Yamamoto M, Mohideen SS, Kitoh J, Ichihara G
  • Journal Title: Toxicol Sci Volume: 115 Pages: 596-606
  • DOI: doi:10.1093/toxsci/kfq075
  • Peer Reviewed
• [Journal Article] Proteinase K-resistant alpha-synuclein is deposited in presynapses in human Lewy body disease and A53T alpha-synuclein transgenic mice (2010)
  • Author(s): Tanji K, Mori F, Mimura J, Itoh K, Kakita A, Takahashi H, Wakabayashi
  • Journal Title: Acta Neuropathol Volume: 120 Pages: 145-154
  • DOI: doi:10.1007/s00401-010-0676-z
  • Peer Reviewed
• [Journal Article] Suppression of AhR signaling pathway is associated with the downregulation of UDP-glucuronosyltransferases during BBN-induced urinary bladder carcinogenesis in mice (2010)
  • Author(s): Iida K, Mimura J, Itoh K, Ohyama C, Fujii-Kuriyama Y, Shimazui T, Akaza H and Yamamoto M
  • Journal Title: J Biochem Volume: 147 Pages: 353-360
  • DOI: doi: 10.1093/jb/mvp169
  • Peer Reviewed
• [Journal Article] Role of Nrf2 and p62/ZIP in the neurite outgrowth by carnosic acid in PC12h cells (2010)
  • Author(s): Kosaka K, Mimura J, Itoh K, Satoh T, Shimojo Y, Kitajima C, Maruyama A, Yamamoto M, Shirasawa T
  • Journal Title: J Biochem Volume: 147 Pages: 73-81
  • DOI: doi:10.1093/jb/mvp149
  • Peer Reviewed
• [Journal Article] Heavy ion beam irradiation regulates the mRNA expression in megakaryocytopoiesis from human hematopoietic stem/progenitor cells (2009)
  • Author(s): Monzen S, Takahashi K, Yoshino H, Kasai-Eguchi K, Abe Y, Maruyama A, Itoh K, Kashiwakura I
  • Journal Title: Radiat Res (Tokyo) Volume: 50 Pages: 477-486
  • URL: http://www.ncbi.nlm.nih.gov/pubmed/19628925
  • Peer Reviewed
• [Journal Article] Lansoprazole, a proton pump inhibitor, mediates anti-inflammatory effect in gastric mucosal cells through the induction of heme oxygenase-1 via activation of NF-E2-related factor 2 and oxidation of kelch-like ECH-associating protein 1 (2009)
  • Author(s): Takagi T, Naito Y, Okada H, Ishii T, Mizushima K, Akagiri S, Adachi S, Handa O, Kokura S, Ichikawa H, Itoh K, Yamamoto M, Matsui H, Yoshikawa T
  • Journal Title: J Pharmacol Exp Ther Volume: 331 Pages: 255-264
  • DOI: doi:10.1124/jpet.109.152702
  • Peer Reviewed
• [Journal Article] Essential role of Nrf2 in keratinocyte protection from UVA by quercetin (2009)
  • Author(s): Kimura S, Warabi E, Yanagawa T, Ma D, Itoh K, Ishii Y, Kawachi Y, Ishii T
  • Journal Title: Biochem Biophys Res Commun Volume: 387 Pages: 109-114
  • DOI: doi:10.1016/j.bbrc.2009.06.136
  • Peer Reviewed
• [Journal Article] Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer (2009)
  • Author(s): Homma S, Ishii Y, Morishima Y, Yamadori T, Matsuno Y, Haraguchi N, Kikuchi N, Satoh H, Sakamoto T, Hizawa N, Itoh K, Yamamoto M
  • Journal Title: Clin Cancer Res Volume: 15 Pages: 3423-3432
  • DOI: doi:10.1158/1078-0432.CCR-08-2822
  • Peer Reviewed
• [Journal Article] Transcription factor Nrf2 mediates an adaptive response to sulforaphane that protects fibroblasts in vitro against the cytotoxic effects of electrophiles, peroxides and redox-cycling agents (2009)
  • Author(s): Higgins LG, Kelleher MO, Eggleston IM, Itoh K, Yamamoto M, Hayes JD
  • Journal Title: Toxicol Appl Pharmacol Volume: 237 Pages: 267-280
  • DOI: doi:10.1016/j.taap.2009.03.005
  • Peer Reviewed
• [Journal Article] Keap1/Nrf2 system regulates neuronal survival as revealed through study of keap1 gene-knockout mice (2009)
  • Author(s): Satoh T, Harada N, Hosoya T, Tohyama K, Yamamoto M, Itoh K
  • Journal Title: Biochem Biophys Res Commun Volume: 380 Pages: 298-302
  • DOI: doi:10.1016/j.bbrc.2009.01.063
  • Peer Reviewed
• [Journal Article] Comparison of citrus coumarins on carcinogen-detoxifying enzymes in Nrf2 knockout mice (2009)
  • Author(s): Prince M, Li Y, Childers A, Itoh K, Yamamoto M, Kleiner HE
  • Journal Title: Toxicol Lett Volume: 185 Pages: 180-186
  • DOI: doi:10.1016/j.toxlet.2008.12.014
  • Peer Reviewed
• [Journal Article] Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice (2008)
  • Author(s): Yoh K, Hirayama A, Ishizaki K, Yamada A, Takeuchi M, Yamagishi S, Morito N, Nakano T, Ojima M, Shimohata H, Itoh K, Takahashi S, Yamamoto M
  • Journal Title: Genes Cells Volume: 13 Pages: 1159-1170
  • DOI: doi:10.1111/j.1365-2443.2008.01234.x
  • Peer Reviewed
• [Journal Article] Nrf2 regulates the alternative first exons of CD36 in macrophages through specific antioxidant response elements (2008)
  • Author(s): Maruyama A, Tsukamoto S, Nishikawa K, Yoshida A, Harada N, Motojima K, Ishii T, Nakane A, Yamamoto M, Itoh K
  • Journal Title: Arch Biochem Biophys Volume: 477 Pages: 139-145
  • DOI: doi:10.1016/j.abb.2008.06.004
  • Peer Reviewed
• [Journal Article] Keap1 Regulates the Constitutive Expression of GST A1 during Differentiation of Caco-2 Cells (2008)
  • Author(s): Kusano Y, Horie S, Shibata T, Satsu H, Shimizu M, Hitomi E, Nishida M, Kurose H, Itoh K, Kobayashi A, Yamamoto M, Uchida K
  • Journal Title: Biochemistry Volume: 47 Pages: 6169-77
  • DOI: doi:10.1021/bi800199z
  • Peer Reviewed
• [Journal Article] A Possible Role of Nrf2 in Prevention of Renal Oxidative Damage by Ferric Nitrilotriacetate (2008)
  • Author(s): Kanki K, Umemura T, Kitamura Y, Ishii Y, Kuroiwa Y, Kodama Y, Itoh K, Yamamoto M, Nishikawa A, Hirose M
  • Journal Title: Toxicol Pathol Volume: 36 Pages: 353-361
  • DOI: doi:10.1177/0192623307311401
  • Peer Reviewed
• [Presentation] アミノ酸飢餓応答因子GCN1L1によるNrf2活性制御機構の解析 (2012)
  • Author(s): 伊東健、他
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 福岡国際会議場(福岡)
  • Year and Date: 20121214-16
• [Presentation] Nrf2 in the bone marrow-derived cells is essential for the high-fat diet induced atherosclerotic plaque formation (2012)
  • Author(s): Ken Itoh, et al.
  • Organizer: 37^<th> FEBS meeting
  • Place of Presentation: Seville Conference and Exhibition Center (Seville, Spain)
  • Year and Date: 20120904-09
• [Presentation] Nrf2 in the bone marrow-derived cells contributes to the high-fat diet induced atherosclerotic plaque formation (2012)
  • Author(s): Ken Itoh, et al.
  • Organizer: THE 33^<RD> NAITO CONFERENCE ON Oxygen Biology: Hypoxia, Oxidative Stress and Diseases
  • Place of Presentation: CHATERAISE Gateaux Kingdom SAPPORO, Sapporo
  • Year and Date: 20120626-29
• [Presentation] Nrf2 in the bone marrow-derived cells is essential for the high-fat diet induced atherosclerotic plaque formation (2012)
  • Author(s): Ken Itoh, et al.
  • Organizer: UK-Japan Research Symposium Molecular Mechanisms of Stress Response in Disease
  • Place of Presentation: Science Information Center, Tsukuba
  • Year and Date: 20120406-07
• [Presentation] The role of ribosome intera-cting protein GCN1L1 in oxidative stress-mediated Nrf2 activation. International symposium 2012 on Signaling (2012)
  • Author(s): Ken Itoh
  • Organizer: Function of Reactive Oxygen Species
  • Place of Presentation: Kyushu University Station-I for Collaboration Research (Fukuoka)
  • Year and Date: 2012-12-17
• [Presentation] Redox-sensitive transcription factor Nrf2 regulates Fpn1-mediated iron efflux and counteracts LPS-mediated Fpn1 mRNA suppression (2011)
  • Author(s): Ken Itoh
  • Organizer: 36^<th> FEBS CONGRESS Biochemistry for Tomorrow's Medicine
  • Place of Presentation: Torino Italy
  • Year and Date: 20110625-26
• [Presentation] Nrf2はヒトHO-1遺伝子プロモーター領域のZ-DNA形成を誘導する (2010)
  • Author(s): 丸山 敦史、伊東 健
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド、神戸
  • Year and Date: 20101207-10
• [Presentation] Role of Nrf2 in the Neurotropic Action of Electrophiles (2010)
  • Author(s): Ken Itoh
  • Organizer: The 9^<th> International Symposium on 'Recent Trends in Pharmaceutical Sciences', February 4 2010
  • Place of Presentation: Institute for Drug Research Yeungnam University, Gyeongsan, Korea
  • Year and Date: 2010-02-04
• [Presentation] Nrf2経路を介した活性酸素シグナル制御機構の解析 (2009)
  • Author(s): 伊東 健
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド、神戸
  • Year and Date: 20091021-24
• [Presentation] Nrf2 co-activator for HO-1 gene regulation (2009)
  • Author(s): Ken Itoh
  • Organizer: 6^<th> International Congress on Heme Oxygenases
  • Place of Presentation: Miami Beach, Florida, USA
  • Year and Date: 20090930-1004
• [Presentation] Role of Nrf2 in neural protection and differentiation (2009)
  • Author(s): Ken Itoh
  • Organizer: SFRR International Free Radical School in Japan, 2009
  • Place of Presentation: JOETSU KOKUSAI SKI RESORT, Echigoyuzawa
  • Year and Date: 20090902-06
• [Presentation] Elucidation of Nrf2-mediated Transactivation Mechanisms (2009)
  • Author(s): Ken Itoh
  • Place of Presentation: Gonryo-kaikan in Tohoku University, Sendai
  • Year and Date: 20090209-11
• [Presentation] Nrf2-HO-1経路の制御機構と生理機能 (2009)
  • Author(s): 伊東 健
  • Organizer: 第6回Heme Oxygenase研究フオーラム
  • Place of Presentation: 京都府立大学・青蓮会館、京都
  • Year and Date: 2009-08-28
• [Presentation] Specific roles of BRG1 and actin-related motif in Nrf2 mediated heme oxygenase-1 induction (2008)
  • Author(s): Ken Itoh, et al.
  • Organizer: BMB2008
  • Place of Presentation: Port Island KOBE, Kobe
  • Year and Date: 2008-12-11
• [Remarks]
  • URL: http://www.med.hirosaki-u.ac.jp/~admed/department/index.html