Elucidation of defensive mechanisms against oxidative stress and search of novel antioxidative substances

2010 Fiscal Year Final Research Report

• Project/Area Number: 21790070
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Kyoto University
• Principal Investigator: IZUMI Yasuhiko Kyoto University, 薬学研究科, 助教 (60456837)
• Project Period (FY): 2009 – 2010
• Keywords: 酸化ストレス / Nrf2-ARE経路

Research Abstract

Nuclear erythroid 2 p45-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway, which induces expression of antioxidant proteins, is a cellular response to oxidative stress. In this study, we clarified the regulatory mechanisms of Nrf2-ARE system and identified a novel activator. First, we examined the effect of bioactive substances on Nrf2-ARE activation by sulforaphan, which is a well-known activator. We found that retinoic acid enhanced sulforaphan-induced ARE activation. Second, we identified a novel activator from extract of Perilla frutescens and clarified the protective effect against 6-hydroxydopamine-induced cell death.

Research Products

• [Journal Article] Glutathione biosynthesis via activation of the nuclear factor E2-related factor 2 (Nrf2)-antioxidant-response element (ARE) pathway is essential for neuroprotective effects of sulforaphane and 6-(methylsulfinyl) hexyl isothiocyanate. (2011)
  • Author(s): Mizuno, K., Kume, T., Muto, C., Takada-Takatori, Y., Izumi, Y., Sugimoto, H., Akaike, A.
  • Journal Title: J.Pharmacol.Sci. 115 Pages: 320-328
  • Peer Reviewed
• [Journal Article] Reconstruction and quantitative evaluation of dopaminergic innervation of striatal neurons in dissociated primary cultures. (2010)
  • Author(s): Wakita, S., Izumi, Y., Matsuo, T., Kume, T., Takada-Takatori, Y., Sawada, H.Akaike, A.
  • Journal Title: J.Neurosci.Methods. 192 Pages: 83-89
  • Peer Reviewed
• [Journal Article] Protective effect of aripiprazole against glutamate cytotoxicity in dopaminergic neurons of rat mesencephalic cultures. (2010)
  • Author(s): Matsuo, T., Izumi, Y., Kume, T., Takada-Takatori, Y., Sawada, H.Akaike, A.
  • Journal Title: Neurosci. Lett. 481 Pages: 78-81
  • Peer Reviewed
• [Journal Article] Heme oxygenase-1 contributes to pathology associated with thrombin-induced striatal and cortical injury in organotypic slice culture. (2010)
  • Author(s): Ohnishi, M., Katsuki, H., Unemura, K., Izumi, Y., Kume, T., Takada-Takatori, Y.Akaike, A.
  • Journal Title: Brain Res. 1347 Pages: 170-178
  • Peer Reviewed
• [Journal Article] Mitogen-activated protein kinases support survival of activated microglia that mediate thrombin-induced striatal injury in organotypic slice culture. (2010)
  • Author(s): Ohnishi, M., Katsuki, H., Izumi, Y., Kume, T., Takada-Takatori, Y.Akaike, A.
  • Journal Title: J.Neurosci.Res. 88 Pages: 2155-2164
  • Peer Reviewed
• [Journal Article] Haloperidol, spiperone, pimozide and aripiprazole reduce intracellular dopamine content in PC12 cells and rat mesencephalic cultures : Implication of inhibition of vesicular transport. (2010)
  • Author(s): Matsuo, T., Izumi, Y., Wakita, S., Kume, T., Takada-Takatori, Y., Sawada, H.Akaike, A.
  • Journal Title: Eur.J.Pharmacol. 640、 Pages: 68-74
  • Peer Reviewed
• [Journal Article] Depolarizing stimuli cause persistent and selective loss of orexin in rat hypothalamic slice culture. (2010)
  • Author(s): Katsuki, H., Kurosu, S., Michinaga, S., Hisatsune, A., Isohama, Y., Izumi, Y., Kume, T.Akaike, A.
  • Journal Title: Peptides 31 Pages: 1131-1138
  • Peer Reviewed
• [Journal Article] Elevation of heme oxygenase-1 by proteasome inhibision affords dopaminergic neuroprotection. (2010)
  • Author(s): Yamamoto, N., Izumi, Y., Matsuo, T., Wakita, S., Kume, T., Takada-Takatori, Y., Sawada, H.Akaike, A.
  • Journal Title: J.Neurosci.Res. 88 Pages: 1934-1942
  • Peer Reviewed
• [Journal Article] Mechanisms of chronic nicotine treatment-induced enhancement of the sensitivity of cortical neurons to the neuroprotective effect of donepezil in cortical neurons. (2010)
  • Author(s): Takada-Takatori, Y., Kume, T., Izumi, Y., Niidome, T., Fujii, T., Sugimoto, H.Akaike, A.
  • Journal Title: J.Pharmacol.Sci. 112 Pages: 265-272
  • Peer Reviewed
• [Journal Article] Dopamine facilitates .-synuclein oligomerization in human neuroblastoma SH-SY5Y cells. (2010)
  • Author(s): Yamakawa, K., Izumi, Y., Takeuchi, H., Yamamoto, N., Kume, T., Akaike, A., Takahashi, R., Shimohama, S.Sawada, H.
  • Journal Title: Biochem. Biophys.Res. Commun. 391 Pages: 129-134
  • Peer Reviewed
• [Journal Article] Mechanisms of neuroprotective effects of nicotine and acetylcholinesterase inhibitors : role of α4 and α7 receptors in neuroprotection. (2010)
  • Author(s): Akaike, A., Takada-Takatori, Y., Kume, T.Izumi, Y.
  • Journal Title: J.Mol.Neurosci. 40 Pages: 211-216
  • Peer Reviewed
• [Presentation] パラコート誘発細胞死における細胞内ヘムの関与 (2011)
  • Author(s): 山本隆盛, 泉安彦, 江角将之, 久米利明, 赤池昭紀
  • Organizer: 日本薬学会第131年会
  • Place of Presentation: 静岡、グランシップツインメッセ静岡
  • Year and Date: 2011-03-30
• [Presentation] PC12細胞における細胞外および細胞内ドパミンに対するクルクミンの作用:細胞膜および小胞モノアミントランスポーターの関与 (2011)
  • Author(s): 松尾剛明, 泉安彦, 久米利明, 金子周司, 澤田秀幸, 杉本八郎, 赤池昭紀
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-03-24
• [Presentation] 培養大脳皮質-線条体切片におけるトロンビン誘発障害とheme oxygenase-1の関与 (2011)
  • Author(s): 大西正俊, 香月博志, 井上敦子, 泉安彦, 久米利明, 赤池昭紀
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-03-23
• [Presentation] ラット心虚血-再灌流障害に対するセロフェンド酸による保護作用 (2011)
  • Author(s): 五百蔵忠明, 赤尾昌治, 久米利明, 井口守丈, 泉安彦, 赤池昭紀
  • Organizer: 第84回日本薬理学会年会
  • Place of Presentation: 横浜パシフィコ横浜
  • Year and Date: 2011-03-23
• [Presentation] Neuroprotective effects of nicotine and acetylcholinesterase inhibitors. (2010)
  • Author(s): Akaike, A., Kume, T., Izumi, Y.
  • Organizer: The 20th Japan-Korea Joint Seminar on Pharmacology
  • Place of Presentation: Kagoshima, Kagoshima Public Center
  • Year and Date: 2010-11-25
• [Presentation] トロンビンによる線条体障害を媒介する活性化ミクログリアにおけるMAPキナーゼの役割 (2010)
  • Author(s): 大西正俊, 香月博志, 井上敦子, 泉安彦, 久米利明, 赤池昭紀
  • Organizer: 第118回日本薬理学会近畿部会
  • Place of Presentation: 大阪千里ライフサイエンスセンター
  • Year and Date: 2010-11-19
• [Presentation] 培養線条体細胞におけるsulforaphaneによるNrf2-ARE経路活性化機構の解明 (2010)
  • Author(s): 水野景太, 久米利明, 大西絵里香, 泉安彦, 赤池昭紀
  • Organizer: 第118回日本薬理学会近畿部会
  • Place of Presentation: 大阪千里ライフサイエンスセンター
  • Year and Date: 2010-11-19
• [Presentation] グルココルチコイドは培養大脳皮質アストロサイトにおいてグルココルチコイド受容体の発現低下を介して細胞増殖を抑制する (2010)
  • Author(s): 畝村和宏, 久米利明, 近藤みなみ, 泉安彦, 赤池昭紀
  • Organizer: 第20回日本臨床精神神経薬理学会第40回日本神経精神薬理学会合同年会
  • Place of Presentation: 仙台市仙台国際センター
  • Year and Date: 2010-09-16
• [Presentation] ロテノンによるタウ蛋白のリン酸化および細胞毒性に関する検討 (2010)
  • Author(s): 本郷春幸, 木原武士, 夏目和明, 泉安彦, 久米利明, 杉本八郎, 赤池昭紀
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム
  • Place of Presentation: 京都市京都大学薬学部
  • Year and Date: 2010-09-11
• [Presentation] アリピプラゾールによるグルタミン酸誘発ドパミンニューロン死に対する保護作用機序の解明 (2010)
  • Author(s): 松尾剛明, 泉安彦, 久米利明, 澤田秀幸, 赤池昭紀
  • Organizer: 次世代を担う創薬・医療薬理シンポジウム
  • Place of Presentation: 京都市京都大学薬学部
  • Year and Date: 2010-09-11
• [Presentation] ラット初代培養心筋細胞における酸化ストレスに対するsulforaphaneの保護作用機序の解析 (2010)
  • Author(s): 久米利明, 市川茉莉那, 泉安彦, 赤池昭紀
  • Organizer: 第117回日本薬理学会近畿部会
  • Place of Presentation: 徳島徳島県郷土文化会館
  • Year and Date: 2010-07-08
• [Presentation] Reconstruction of the nigrostriatal projections in dissociated primary cultures : A role of striatal cells in dopaminergic neurite outgrowth. (2010)
  • Author(s): Wakita, S., Izumi, Y., Kume, T., Sawada, H., Akaike, A.
  • Organizer: World Pharma 2010
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2010-06-19
• [Presentation] Neuroprotective effect of serofendic acid on in vitro and in vivo neuronal injury. (2010)
  • Author(s): Kume, T., Izumi, Y., Akaike, A.
  • Organizer: World Pharma 2010
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2010-06-19
• [Presentation] Paraquat activates Nrf2-ARE pathway : implication of decrease in proteasome activity in dopamine-mediated cytotoxicity. (2010)
  • Author(s): Izumi, Y., Matsushima, S., Yamamoto, N., Kume, T., Sawada, H., Akaike, A.
  • Organizer: World Pharma 2010
  • Place of Presentation: Copenhagen, Denmark
  • Year and Date: 2010-06-19