A role for the aryl hydrocarbon receptor in regulation of ischemia-induced angiogenesis

• Project/Area Number: 18590553
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Hygiene
• Research Institution: Mie University
• Principal Investigator: ICHIHARA Sahoko Mie University, 生命科学研究支援センター, 助教 (20378326)
• Co-Investigator(Kenkyū-buntansha): YAMADA Yoshiji 三重大学, 生命科学研究支援センター, 教授 (90333286) ; 室原 豊明 名古屋大学, 医学系研科, 教授 (90299503) ; 市原 学 名古屋大学, 医学系研科, 准教授 (90252238)
• Co-Investigator(Renkei-kenkyūsha): MUROHARA Toyoaki 名古屋大学, 医学系研究科, 教授 (90299503) ; ICHIHARA Gaku 名古屋大学, 医学系研究科, 准教授 (90252238)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,140,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥540,000); Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
• Keywords: アレルハイドロカーボン受容体 / 喫煙 / 血管新生 / 酸化ストレス / ベンツピレン / 末梢血管障害 / 核内受容体 / アリルハイドロカーボン / 低酸素 / 転写因子

Research Abstract

タバコの粒子相成分の1つであるベンツピレン等が結合するアレルハイドロカーボン受容体(Ah 受容体)に着目し、喫煙に起因する疾患発症や進展過程における分子メカニズムの解明を行った。Ah受容体が欠損すると、Ah 受容体と2量体を形成するARNT が低酸素反応性因子であるHIF1A との2量体形成に移行し、血管内皮細胞増殖因子の転写活性を高めることにより、血管新生を促進することを見出した。

Research Products

• [Journal Article] Inhibition of ischemia-induced angiogenesis by benzo[a]pyrene in a manner dependent on the aryl hydrocarbon receptor (2009)
  • Author(s): Ichihara S, Yamada Y, Gonzalez FJ, Nakajima T, Murohara T, Ichihara G.
  • Journal Title: Biochem Biophys Res Commun 381(1) Pages: 44-49
  • Peer Reviewed
• [Journal Article] Inhibition of ischemia-induced angiogenesis by benzo [a] pyrene in a manner dependent on the aryl hydrocarbon receptor. (2009)
  • Author(s): Ichihara S, Yamada Y, Gonzalez FJ, Nakajima T, Murohara T, Ichihara G.
  • Journal Title: Biochem Biophys Res Commun 381 Pages: 44-49
  • Peer Reviewed
• [Journal Article] Association of polymorphism of ABCA1 with obesity in Japanese individuals (2008)
  • Author(s): Ichihara S, Yamada Y, Kato K, Hibino T, Yokoi K, Matsuo H, Kojima T, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y.
  • Journal Title: Genomics 91(6) Pages: 512-516
  • Peer Reviewed
• [Journal Article] Association of genetic variants with atherothrombotic cerebral in farction in Japanese individuals with metabolic syndrome. (2008)
  • Author(s): Yamada Y, Kato K, Oguri M, Yoshida T, Yokoi K, Watanabe S, Metoki N, Yoshida H, Satoh K, Ichihara S, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y.
  • Journal Title: Int J Mol Med 21 Pages: 801-808
  • Peer Reviewed
• [Journal Article] Association of polymorphism of ABCB1 with obesity in Japanese individuals. (2008)
  • Author(s): Ichihara S, Yamada Y, Kato K, Hibino T, Yokoi K, Matsuo H, Kojima T, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y.
  • Journal Title: Genomics 91 Pages: 512-516
  • Peer Reviewed
• [Journal Article] Genetic factors for ischemic and hemorrhagic stroke in Japanese individuals. (2008)
  • Author(s): Yamada Y, Metoki N, Yoshida H, Satoh K, Kimihiko Kato, Takeshi Hibino, Kiyoshi Yokoi, Sachiro Watanabe, Ichihara S, Yukitoshi Aoyagi, Akitomo Yasunaga, Hyuntae Park, Masashi Tanaka, Yoshinori Nozawa.
  • Journal Title: Stroke 39 Pages: 2211-2218
  • Peer Reviewed
• [Journal Article] Association of polymorphisms of ABCA1 and ROS1 with hyper-tension in Japanese individuals. (2008)
  • Author(s): Yamada Y, Kato K, Yoshida T, Yokoi K, Matsuo H, Watanabe S, Ichihara S, Metoki N, Yoshida H, Satoh K, Aovagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y.
  • Journal Title: Int J Mol Med 21 Pages: 83-89
  • Peer Reviewed
• [Journal Article] Genetic risk for myocardial infarction determined by polymer-phisms of candidate genes in Japanese individuals. (2008)
  • Author(s): Yamada Y, Kato K, Oguri M, Fujimaki T, Yokoi K, Matsuo H, Watanabe S, Metoki N, Yoshida H, Satoh K, Ichihara S, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Nozawa Y.
  • Journal Title: J Med Genet 45 Pages: 216-221
  • Peer Reviewed
• [Journal Article] Genetic factors for human obesity. (2008)
  • Author(s): Ichihara S, Yamada Y.
  • Journal Title: Cell Mol Life Sci 65 Pages: 1086-1098
  • Peer Reviewed
• [Journal Article] Genetic risk for metabolic syndrome : examination of candidate gene polymorphisms related to lipid metabolism in Japanese individuals. (2008)
  • Author(s): Yamada Y, Ichihara S, Kato K, Yoshida T, Yokoi K, Matsuo H, Watanabe S, Metoki N, Yoshida H, Satoh K, Ichihara S, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Lee W, Nozawa Y.
  • Journal Title: J Med Genet 45 Pages: 22-28
  • Peer Reviewed
• [Journal Article] Reversibility of the Adverse Effects of 1-Bromopropane Exposure in Rats (2007)
  • Author(s): Banu S, Ichihara S, Huang F, Ito H, Inaguma Y, Furuhashi K, Fukunaga Y, Wang Q, Kitoh J, Ando H, Kikkawa F, Ichihara G.
  • Journal Title: Toxicol Sci 100(2) Pages: 504-512
  • Peer Reviewed
• [Journal Article] Differential cardiovascular effects of endotoxin derived from Escherichia coli or Pseudomonas aeruginosa (2007)
  • Author(s): Matsushita A, Iwase M, Kato Y, Ichihara S, Ichihara G, Kimata H, Hayashi K, Hashimoto K, Yokoi T, Noda A, Koike Y, Yokota M, Nagata K
  • Journal Title: Exp Anim 56(5) Pages: 339-348
  • NAID: 130000068018
  • Peer Reviewed
• [Journal Article] Roles of oxidative stress and Akt signaling in doxorubicin cardiotoxicity (2007)
  • Author(s): Ichihara S, Yamada Y, Kawai Y, Osawa T, Furuhashi K, Duan Z, Ichihara G.
  • Journal Title: Biochem Biophys Res Commun 359(1) Pages: 27-33
  • Peer Reviewed
• [Journal Article] A role for the aryl hydrocarbon receptor in regulation of ischemia-induced angiogenesis (2007)
  • Author(s): Ichihara S, Yamada Y, Ichihara G, Nakajima T, Kondo T, Gonzalez FJ, Murohara T.
  • Journal Title: Arterioscler Thromb Vasc Biol 27(6) Pages: 1297-1304
  • Peer Reviewed
• [Journal Article] A Role for the Aryl Hydrocarbon Receptor in Regulation of Ischemia-Induced Angiogenesis (2007)
  • Author(s): Ichihara S, et. al.
  • Journal Title: Arterioscler.Thromb.Vase.Biol. 2007;27 Pages: 1297-1304
  • Peer Reviewed
• [Journal Article] Roles of Oxidative Stress and Akt Signaling in Doxorubicin Cardiotoxicity (2007)
  • Author(s): Icluhara S, et. al.
  • Journal Title: Biochem.Biophys.Res.Commun. 2007;359 Pages: 27-33
  • Peer Reviewed
• [Journal Article] Therapeutic angiogenesis using novel vascular endothelial growth factor-E/human placental growth factor chimera genes. (2007)
  • Author(s): Inoue N, Kondo T, Kobayashi K, Aoki M, Numaguchi Y, Shibuya M, Murohara T
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology 27 Pages: 99-105
• [Journal Article] Attenuation of oxidative stress and cardiac dysfunction by bisoprolol in an animal model of dilated cardiomyopathy (2006)
  • Author(s): Ichihara S, Yamada Y, Ichihara G, Kanazawa H, Hashimoto K, Kato Y, Matsushita A, Oikawa S, Yokota M, Iwase M.
  • Journal Title: Biochem Biophys Res Commun 350(1) Pages: 105-113
  • Peer Reviewed
• [Journal Article] Attenuation of ventricular hypertrophy and fibrosis in rats by pitavastatin : potential role of RhoA-extracellular signal-regulated kinase- serum response factor signaling pathway (2006)
  • Author(s): Saka M, Obata K, Ichihara S, Cheng XW, Kimata H, Noda A, Izawa H, Nagata K, Yokota M
  • Journal Title: Clin Exp Pharmacol Physiol 33(12) Pages: 1164-1171
  • Peer Reviewed
• [Journal Article] Attenuation of cardiac dysfunction by a PPAR-alpha agonist is associated with down-regulation of redox-regulated transcription factors (2006)
  • Author(s): Ichihara S, Obata K, Yamada Y, Nagata K, Noda A, Ichihara G, Yamada A, Kato T, Izawa H, Murohara T, Yokota M.
  • Journal Title: J Mol Cell Cardiol 41(2) Pages: 318-329
  • Peer Reviewed
• [Journal Article] Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure (2006)
  • Author(s): Saka M, Obata K, Ichihara S, Cheng XW, Kimata H, Nishizawa T, Noda A, Izawa H, Nagata K, Murohara T, Yokota M.
  • Journal Title: J Cardiovasc Pharmacol 47(6) Pages: 770-779
  • Peer Reviewed
• [Journal Article] Effects of exposure of rat dams to 1-bromopropane during pregnancy and lactation on growth and sexual maturation of their offspring (2006)
  • Author(s): Furuhashi K, Kitoh J, Tsukamura H, Maeda KI, Wang H, Li W, Ichihara S, Nakajima T, Ichihara G.
  • Journal Title: Toxicology 224 : (3) Pages: 219-228
  • Peer Reviewed
• [Journal Article] Mineralocorticoid receptor antagonism attenuates cardiac hypertrophy and failure in low-aldosterone hypertensive rats (2006)
  • Author(s): Nagata K, Obata K, Xu J, Ichihara S, Noda A, Kimata H, Kato T, Izawa H, Murohara T, Yokota M.
  • Journal Title: Hypertension 47(4) Pages: 656-664
  • NAID: 130004245524
  • Peer Reviewed
• [Journal Article] Attenuation of cardiac dysfunction by a PPAR-α agonist is associated with down-regulation of redox-regulated transcription factors. (2006)
  • Author(s): Ichihara S, Obata K, Yamada Y, Nagata K, Noda A, Ichihara G, Yamada A, Kato T, Murohara T, Yokota M
  • Journal Title: Journal of Molecular Cellular Cardiology 41 Pages: 318-329
• [Journal Article] Effects of exposure of rat dams to 1-bromopropane during pregnancy and lactation on growth and sexual maturation of their offspring. (2006)
  • Author(s): Furuhashi K, Kitoh J, Tsukamura H, Maeda KI, Wang H, Li W, Ichihara S, Nakajima T, Ichihara G
  • Journal Title: Toxicology 224 Pages: 219-228
• [Journal Article] Combination of in vivo angiopoietin-1 gene transfer and autologous bone marrow cell implantation for functional therapeutic angiogenesis. (2006)
  • Author(s): Kobayashi K, Kondo T, Inoue N, Aoki M, Mizuno M, Komori K, Yoshida J, Murohara T
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology 26 Pages: 1465-1472
• [Journal Article] Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure. (2006)
  • Author(s): Saka M, Obata K, Ichihara S, Cheng XW, Kimata H, Nishizawa T, Noda A, Izawa H, Murohara T, Nagata K, Yokota M
  • Journal Title: Journal of Cardiovascular Pharmacology 47 Pages: 770-779
• [Journal Article] Attenuation of oxidative stress and cardiac dysfunction by bisoprclol in an animal model of dilated cardiomyopathy. (2006)
  • Author(s): Ichihara S, Yamada Y, Ichihara G, Kanazawa H, Hashimoto K, Kato Y, Matsushita A, Oikawa S, Yokota M, Iwase M
  • Journal Title: Biochemical and Biophysical Research Communications 350 Pages: 105-113
• [Presentation] Inhibition of ischemia-induced angiogenesis by benzo[a]pyrene in a manner dependent on the aryl hydrocarbon receptor (2009)
  • Author(s): Sahoko Ichihara, Yoshiji Yamada, Gaku Ichihara, Tamie Nakajima, Frank J Gonzalez, Toyoaki Murohara
  • Organizer: The 48th Annual Meeting of the Society of Toxicology
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2009-03-16
• [Presentation] Inhibition of ischemia-induced angiogenesis by benzo[a]pyrene in a manner dependent on the aryl hydrocarbon receptor. (2009)
  • Author(s): Sahoko Ichihara. Yoshiji Yamada, Gaku Ichihara, Tamie Nakajima, Frank J Gonzalez, Toyoaki Murohara.
  • Organizer: The 48th Annual Meeting of the Society of Toxicology
  • Place of Presentation: Baltimore, USA
  • Year and Date: 2009-03-16
• [Presentation] Ablation of Nrf2 resulted in enhancement of ischemia-induced angiogenesis (2008)
  • Author(s): Sahoko Ichihara, Gaku Ichihara, Fang Liu, Toyoaki Murohara, Yoshiji Yamada
  • Organizer: The 81th Scientific Sessions of American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-11
• [Presentation] Ablation of Nrf2 resulted in enhancement of ischemia-induced angiogenesis. (2008)
  • Author(s): Sahoko Ichihara, Gaku Ichihara, Fang Liu, Toyoaki Murohara, Yoshiji Yamada.
  • Organizer: The 81th Scientific Sessions of American Heart Association
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2008-11-11
• [Presentation] Research strategy for cardiovascular effects of manufactured nanomaterials (2008)
  • Author(s): Sahoko Ichihara
  • Organizer: China-Japan Collaboration Workshop
  • Place of Presentation: Shanghai, China
  • Year and Date: 2008-07-31
• [Presentation] Cardiovascular effects of 1-bromopropane (2008)
  • Author(s): Sahoko Ichihara
  • Organizer: China-Japan Collaboration Workshop
  • Place of Presentation: Shanghai, China
  • Year and Date: 2008-07-30
• [Presentation] Cardiovascular effects of I-bromopropane. (2008)
  • Author(s): Sahoko Ichihara.
  • Organizer: China-Japan Collaboration Workshop
  • Place of Presentation: Shanghai, China
  • Year and Date: 2008-07-30
• [Presentation] 1-ブロモプロパンの曝露による神経伝達物質受容体遺伝子発現への影響解析と中枢神経毒性バイオマーカーの開発 (2008)
  • Author(s): シェイク モヒディーン サハブディーン, 市原佐保子, 劉芳, 古橋功一, 李衛華, 市原学
  • Organizer: 第81回日本産業衛生学会
  • Place of Presentation: 札幌、日本
  • Year and Date: 2008-06-25
• [Presentation] 1-ブロモプロパン曝露労働者の量依存的な神経系、血管系影響 (2008)
  • Author(s): 李衛華, 柴田英治, 王強毅, 市原佐保子, 丁訓誠, 竹内康浩, 市原学
  • Organizer: 第81回日本産業衛生学会
  • Place of Presentation: 札幌、日本
  • Year and Date: 2008-06-25
• [Presentation] Effect of 1-bromopropane exposure on gene expression of neurotransmitter receptors in rat (2008)
  • Author(s): S. Sheik Mohideen, Sahoko Ichihara, F. Liu, Koichi. Furuhashi, Weihua Li, Gaku Ichihara
  • Organizer: The 47th Annual Meeting of Society of Toxicology
  • Place of Presentation: Seattle, USA
  • Year and Date: 2008-03-18
• [Presentation] Protective effect of metallothionein in ischemic hindlimb against oxidative stress induced by benzo[a]pyrene (2007)
  • Author(s): Sahoko Ichihara, Gaku Ichihara, Toyoaki Murohara, Yoshiji Yamada
  • Organizer: The 80th Scientific Sessions of American Heart Association
  • Place of Presentation: Orlando, USA
  • Year and Date: 2007-11-07
• [Presentation] DNA microarray study with two dimensional analysis on susceptibility to 1-bromopropane exposure (2007)
  • Author(s): Fen Huang, Sahoko Ichihara, Emiko Kitagawa, Satomi Mizukami, Hitoshi Iwahashi, Junzoh Kitoh, Koichi Furuhashi, Shameema Banu, Mari Iida, Gaku Ichihara
  • Organizer: International Congress of Toxicology
  • Place of Presentation: Montreal, Canada
  • Year and Date: 2007-07-17
• [Presentation] Reversibility of the adverse effects of 1-bromopropane exposure in rats (2007)
  • Author(s): Shameema Banu, Sahoko Ichihara, Fen Huang, Hidenori Ito, Yutaka Inaguma, Koichi Furuhashi, Suminobu Fukunaga, Qiangyi Wang, Gaku Ichihara
  • Organizer: The 46th Annual Meeting of Society of Toxicology
  • Place of Presentation: Charlotte, USA
  • Year and Date: 2007-03-26
• [Presentation] DNA microarray study with two dimensional analysis on susceptibility to 1-bromopropane exposure. (2007)
  • Author(s): Huang F, Ichihara S, et. al.
  • Organizer: International Congress of Toxicology
  • Place of Presentation: Montreal,Canada
• [Presentation] Protective effect of metallothionein in ischemic hindlimb against oxidati-ve stress induced by benzo[a]yrene (2007)
  • Author(s): Ichihara S, et. al.
  • Organizer: The 80th Scientific Sessions of American Heart Association
  • Place of Presentation: Orlando,USA
• [Presentation] Association between glutathione S-transferase gene polymorphism and neural effects in workers exposed to 1-brromopropane (2007)
  • Author(s): 王強毅、市原佐 保子、 等
  • Organizer: 第80回日本産業衛生学会
  • Place of Presentation: 大阪府大阪市
• [Presentation] 1-プロモプロパンの神経伝達物質受容体遺伝子発現への影響と中枢神経影響バイオマーカーの探索 (2007)
  • Author(s): シェイク モヒディーン ザハブデーン、市原 佐保子, 等
  • Organizer: 平成19年度日本産業衛生学会東海地方会
  • Place of Presentation: 愛知県名古屋市
• [Presentation] Prediction of genetic risk for metabolic syndrome (2006)
  • Author(s): Sahoko Ichihara, Yoshiji Yamada, Kimihiko Kato, Takeshi Hibino, Kiyoshi Yokoi, Hitoshi Matsuo, Tomonori Segawa, Sachiro Watanabe, Hidemi Yoshida, Kei Satoh, Yoshinori Nozawa
  • Organizer: The 79th Scientific Sessions of American Heart Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 2006-11-14
• [Presentation] Regulatory role of hypoxia-inducible factor-1α and redox-regulated transcription factor in doxorubicin cardiotoxicity (2006)
  • Author(s): Sahoko Ichihara, Gaku Ichihara, Yoshichika Kawai, Toshihiko Osawa, Yoshiji Yamada
  • Organizer: The 79th Scientific Sessions of American Heart Association
  • Place of Presentation: Chicago, USA
  • Year and Date: 2006-11-12
• [Presentation] Development of renal injury and lipid metabolic disorder in obese and hypertensive SHR/NDmcr-cp(cp/cp) (2006)
  • Author(s): Kazuya Kitamori, Masashi Kobayashi, Gaku Ichihara, Sahoko Ichihara, Satoshi Tsuchikura, Junko Hiraoka-Yamamoto, Naoto Yasui, Naoko Yasuo, Kohzo Ikeda, Yukio Yamori, Tamie Nakajima
  • Organizer: The 12th International Symposium on SHR
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2006-10-20
• [Presentation] Adverse effects of exposure to 1-bromopropane on central nervous system and perioheral nerve in human (2006)
  • Author(s): Gaku Ichihara, Weihua Li, Eiji Shibata, Xuncheng Ding, Jiefei Li, Hailan Wang Fen Huang, Simeng Peng, Biao Gu, Sahoko Ichihara, Maiko Miyata, Yasuhiro Takeuchi
  • Organizer: The 28th International Congress on Occupational Health
  • Place of Presentation: Milan, Italy
  • Year and Date: 2006-06-13
• [Book] バイオ解析・診断技術のテーラーメイド医療への応用 (2006)
  • Author(s): 市原佐保子, 横田充弘
  • Publisher: シーエムシー出版
• [Remarks]
  • URL: http://www.lsrc.mie-u.ac.jp/human/ichihara_gaiyou.html