Elucidation of neuroprotective mechanisms of low-molecular-weight fetus-specific compounds

• Project/Area Number: 19790054
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: Kyoto University
• Principal Investigator: KUME Toshiaki Kyoto University, 薬学研究科, 准教授 (10303843)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,720,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2007: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: 低分子量化合物 / 生理活性物質 / 脳・神経 / 薬理学

Research Abstract

様々な脳疾患に対する防御機構における低分子生体内機能分子の役割を解明することを目的とし、研究を遂行し下記の成果を得た。胎仔由来神経保護物質であるセロフェンド酸が作用を発現する際に重要なセロフェンド酸結合タンパクの候補を見出した。また、in vivoにおける検討において、セロフェンド酸は尾静脈からの末梢投与においても虚血障害に対して保護的に働くことが明らかとなった。胎仔組織には胎仔期特有の化合物が存在すると推定されるので、保護活性化合物の探索を行ったところ、ウシ胎盤にcaspase-3阻害活性を見出した。

Research Products

• [Journal Article] Mechanism of neuroprotection by donepezil pretreatment in rat cortical neurons chronically treated with donepezil (2008)
  • Author(s): Takada-Takatori, Y., Kume, T., Ohgi, Y., Izumi, Y., Niidome, T., Fujii, T., Sugimoto, H. Akaike, A.
  • Journal Title: J. Neurosci. Res. 86 Pages: 3575-3583
  • Peer Reviewed
• [Journal Article] Bromocriptine, a dopamineD2 receptor agonist with the structure of the amino acid ergot alkaloids, induces neurite outgrowth in PC12 cells (2008)
  • Author(s): Oda, T., Kume, T., Izumi, Y., Takada-Takatori, Y., Niidome, T., Akaike, A.
  • Journal Title: Eur. J. Pharmacol. 598 Pages: 27-31
  • Peer Reviewed
• [Journal Article] Protective effect of serofendic acid on ischemic injury induced by occlusion of the middle cerebral artery in rats (2008)
  • Author(s): Nakamura, T., Kume, T., Katsuki, H., Niidome, T., Sugimoto, H., Akaike, A.
  • Journal Title: Eur. J. Pharmacol. 586 Pages: 151-155
  • Peer Reviewed
• [Journal Article] Regulation of intracellular dopamine levels by dopaminergic drugs: involvement of vesicular monoamine transporter (2008)
  • Author(s): Izumi, Y., Yamamoto, N., Kume, T., Katsuki, H., Sawada, H., Akaike, A.
  • Journal Title: Eur. J. Pharmacol. 582 Pages: 52-61
  • Peer Reviewed
• [Journal Article] Chloride-dependent acute excitotoxicity in adult rat retinal ganglion cells (2008)
  • Author(s): Hama, Y., Katsuki, H., Suminaka, C., Kume, T., Akaike, A.
  • Journal Title: Neuropharm. 55 Pages: 677-686
  • Peer Reviewed
• [Journal Article] Plasminogen potentiates thrombin cytotoxicity and contributes to pathology of intracerebral hemorrhage in rats (2008)
  • Author(s): Fujimoto, S., Katsuki, H., Ohnishi, M., Takagi, M., Kume, T., Akaike, A.
  • Journal Title: J. Cereb. Blood Flow Metab. 28 Pages: 506-515
  • NAID: 120002468476
  • Peer Reviewed
• [Journal Article] Mechanism of neuroprotection by donepezil pretreatment in rat cortical neurons aronically treated with (2008)
  • Author(s): Takada-Takatori, Y., Kume, T., Ohgi, Y., Izumi, Y., Niidome, T., Fujii, T., Sugimoto, H. and Akaike, A.
  • Journal Title: J. Neurosci. Res. 86 Pages: 3575-3583
  • Peer Reviewed
• [Journal Article] Bromocriptine, a dopamine D2 receptor agonist with the structure of the aminoacid ergot alkaloids, induces neurite outgrowth in PC12 cells (2008)
  • Author(s): Oda, T., Kume, T., Izumi, Y., Takada-Takatori, Y., Niidome, T. and Akaike, A.
  • Journal Title: Eur. J. Pharmacol. 598 Pages: 27-31
  • Peer Reviewed
• [Journal Article] Protective effect of serofendic acid on ischemic injury induced by occlusion of the middle cerebral artery in rats (2008)
  • Author(s): Nakamura, T., Kume, T., Katsuki, FL,. Niidome, T., Sugimoto, H. and Akaike, A.
  • Journal Title: Eur. J. Pharmacol. 586 Pages: 151-155
  • Peer Reviewed
• [Journal Article] Regulation of intracellular dopamine levelS by dopaninergic drugs : involvement of vesicular monoamine transporter (2008)
  • Author(s): Izumi, Y., Yamamoto, N., Kume, T., Katsuki, H., Sawada, H. and Akaike, A.
  • Journal Title: Eur. J. Pharmacol. 582 Pages: 52-61
  • Peer Reviewed
• [Journal Article] Chloride-dependent acute excitotoXicity in adult 'rat retinal ganglion cells (2008)
  • Author(s): Hama, Y., Katsuki, H., Suminaka, C., Kume, T. and Akaike, A.
  • Journal Title: Neuropharm 55 Pages: 677-686
  • Peer Reviewed
• [Journal Article] Plasminogen potentiates thrombin cytotoxicity and contributes to pathology of intracerebral hemorrhage in rats (2008)
  • Author(s): Fujimoto, S., Katsuki, H., Ohnishi, M., Takagi, M., Kume, T. and Akaike, A.
  • Journal Title: J. Cereb. Blood Flow Metab 28 Pages: 506-515
  • NAID: 120002468476
  • Peer Reviewed
• [Journal Article] Proteasome inhibition induces glutathione synthesis and protects cells from oxidative stress (2007)
  • Author(s): Yamamoto, N., Sawada, H., Izumi, Y., Kume, T., Katsuki, H., Shimohama, S., Akaike, A.
  • Journal Title: J. Biol. Chem. 282 Pages: 4364-4372
  • Peer Reviewed
• [Journal Article] Synthesis and pharmacological profile of serofendic acids A and B (2007)
  • Author(s): Terauchi, T., Asai, N., Doko, T., Taguchi, R., Takenaka, O., Sakurai, H., Yonaga, M., Kimura, T., Kajiwara, A., Niidome, T., Kume, T., Akaike, A., Sugimoto, H.
  • Journal Title: Bioorg. Med. Chem. 15 Pages: 7098-7107
  • Peer Reviewed
• [Journal Article] Resveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults (2007)
  • Author(s): Okawara, M., Katsuki, H., Kurimoto, E., Shibata, H., Kume, T., Akaike, A.
  • Journal Title: Biochem. Pharmacol. 73 Pages: 550-560
  • NAID: 120002468473
  • Peer Reviewed
• [Journal Article] Involvement of thrombin and mitogen-activated protein kinase pathways in hemorrhagic brain injury (2007)
  • Author(s): Ohnishi, M., Katsuki, H., Fujimoto, S., Takagi, M., Kume, T., Akaike, A.
  • Journal Title: Experimental Neurology 206 Pages: 43-52
  • NAID: 120002468474
  • Peer Reviewed
• [Journal Article] Donepezil potentiates nerve growth factor-induced neurite outgrowth in PC12 cells (2007)
  • Author(s): Oda, T., Kume, T., Katsuki, H., Niidome, T., Sugimoto, H., Akaike, A.
  • Journal Title: J. Pharmacol. Sci. 104 Pages: 349-354
  • NAID: 10024315249
  • Peer Reviewed
• [Journal Article] Contribution of endogenous glycine and D-serine to excitotoxic and ischemic cell death in rat cerebrocortical slice cultures (2007)
  • Author(s): Katsuki, H., Watanabe, Y., Fujimoto, S., Kume, T., Aakike, A.
  • Journal Title: Life Sci. 81 Pages: 740-749
  • Peer Reviewed
• [Journal Article] Novel neuroprotective mechanisms of pramipexole, an anti-Parkinson drug, against endogenous dopamine-mediated excitotoxicity (2007)
  • Author(s): Izumi, Y., Sawada, H., Yamamoto, N., Kume, T., Katsuki, H., Shimohama, S., Akaike, A.
  • Journal Title: Eur. J. Pharmacol. 557 Pages: 132-140
  • Peer Reviewed
• [Journal Article] Thrombin induces striatal Neurotoxicity depending on mitogen-activated protein kinase pathways in vivo (2007)
  • Author(s): Fujimoto, S., Katsuki, H., Ohnishi, M., Takagi, M., Kume, T., Akaike, A.
  • Journal Title: Neurosci. 144 Pages: 694-701
  • NAID: 120002468472
  • Peer Reviewed
• [Journal Article] Serofendic Acid, a substance extracted from fetal calf serum, as a novel drug for cardioprotection (2007)
  • Author(s): Akao, M., Takeda, T., Kita, T., Kume, T., Akaike, A.
  • Journal Title: Cardiovasc Drug Rev. 25 Pages: 333-341
  • Peer Reviewed
• [Journal Article] Serofendic Acid, a substance extracted from fetal calf serum, as a novel drug for cardioprotection (2007)
  • Author(s): Akao, M., Takeda, T., Kita, T., Kume, T. and Akaike,
  • Journal Title: Cardiovasc Drug Rev. 25 Pages: 333-341
  • Peer Reviewed
• [Journal Article] Synthesis and pharmacological profile of serofendic acids A and B. (2007)
  • Author(s): Terauchi, T., Asai, N., Doko, T., Taguchi, R., Takenaka, O., Sakurai, H., Yonaga, M., Kimura, T., Kajiwara, A., Niidome, T., Kume, T., Akaike, A. and Sugimoto, H.
  • Journal Title: Bioorg. Med. Chem. 15 Pages: 7098-7107
  • Peer Reviewed
• [Journal Article] Contribution of endogenous glycine and D-serine to excitotoxic and ischemic cell death in rat cerebrocortical slice cultures. (2007)
  • Author(s): Katsuki, H., Watanabe, Y., Fujimoto, S., Kume, T. and Akaike, A.
  • Journal Title: Life Sci. 81 Pages: 740-749
  • Peer Reviewed
• [Journal Article] Involvement of thrombin and mitogen-activated protein kinase pathwaysin hemorrhagic brain injury・ (2007)
  • Author(s): Ohnishi, M., Katsuki, H., Fujimoto, S., Takagi, M., Kume, T. and Akaike, A.:
  • Journal Title: Experimental Neurology 206 Pages: 43-52
  • Peer Reviewed
• [Journal Article] Donepezil potentiates nerve growth factor-induced neurite outgrowth in PC12 cells. (2007)
  • Author(s): Oda, T., Kume, T., Katsuki, H., Niidome, T., Sugimoto, H. and Akaike, A.
  • Journal Title: J. Pharmacol. Sci. 104 Pages: 349-354
  • NAID: 10024315249
  • Peer Reviewed
• [Journal Article] Resveratrol protects dopaminergic neurons in midbrain slice culture from multiple insults. (2007)
  • Author(s): Okawara, M., Katsuki, H., Kurimoto, E., Shibata, H., Kume, T. and Akaike, A.
  • Journal Title: Biochem. Pharmacol. 73 Pages: 550-560
  • NAID: 120002468473
  • Peer Reviewed
• [Journal Article] Proteasome inhibition induces glutathione synthesis and protects cells from oxidative stress. (2007)
  • Author(s): Yamamoto, N., Sawada, H., Izumi, Y., Kume, T., Katsuki, H., Shimohama, S., Akaike, A.
  • Journal Title: J. Biol. Chem. 282 Pages: 4364-4372
  • Peer Reviewed
• [Journal Article] Thrombin induces striatal Neurotoxicity depending on mitogen-activated protein kinase pathways in vivo. (2007)
  • Author(s): Fujimoto, S., Katsuki, H., Ohnishi, M., Takagi, M., Kume, T. and Akaike, A.
  • Journal Title: Neuroscience 144 Pages: 694-701
  • NAID: 120002468472
  • Peer Reviewed
• [Journal Article] Novel neuroprotective mechanisms of pramipexole, an anti-Parkinson drug, against endogenous dopamine-mediated excitotoxicity. (2007)
  • Author(s): Izumi, Y., Sawada, H., Yamamoto, N., Kume, T., Katsuki, H., Shimohama, S., Akaike, A.
  • Journal Title: Eur. J. Pharmacol. 557 Pages: 132-140
  • Peer Reviewed
• [Presentation] ドネペジル慢性処置による神経保護作用の感受性上昇機序 (2008)
  • Author(s): 高鳥悠記, 久米利明, 大木雄太, 泉安彦, 新留徹広, 藤井健志, 岡部進, 杉本八郎, 赤池昭紀
  • Organizer: 第2回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-12-20
• [Presentation] 培養大脳皮質細胞におけるグルタミン酸神経毒性に対するpitavastatinの保護作用 (2008)
  • Author(s): 大木雄太, 泉安彦, 久米利明, 赤池昭紀
  • Organizer: 第2回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-12-20
• [Presentation] 培養大脳皮質細胞におけるグルダミン酸神経毒性に対するpitavastatinの保護作用 (2008)
  • Author(s): 大木雄太, 泉安彦, 久米利明, 赤池昭紀
  • Organizer: 第2回次世代を担う若手医療薬科学シシポジウム
  • Place of Presentation: 京都
  • Year and Date: 2008-12-20
• [Presentation] 培養神経細胞における果汁・野菜エーテル抽出物の酸化ストレスに対する作用の検討 (2008)
  • Author(s): 武藤千恵, 水野景太, 久米利明, 泉安彦, 赤池昭紀
  • Organizer: 第114回日本薬理学会近畿部会
  • Place of Presentation: 神戸
  • Year and Date: 2008-11-14
• [Presentation] Serofendic acid protects ischemic injury by occlusion of the middle cerebral artery in rats (2008)
  • Author(s): Kume, T., Nakamura, T., Izumi, Y., Akaike, A.
  • Organizer: The 19^<th> Korea-Japan Joint Seminar on Pharmacology
  • Place of Presentation: Busan, Korea
  • Year and Date: 2008-11-07
• [Presentation] Serofendic acid protects isehemic injury by occlusion of the middle cerebral artery in rats (2008)
  • Author(s): Kume, T., Nakamurn, T. Izumi, Y. and Akaike. A.
  • Organizer: The 19th Korea-Japan Joint Seminar on Pharmacology
  • Place of Presentation: Busan, Korea
  • Year and Date: 2008-11-07
• [Presentation] Mechanisms of neuroprotective effects of nicotine and acetylcholinesterase inhibitors: role of alpha4 and alpha7 receptors in neuroprotection (2008)
  • Author(s): Akaike, A., Kume, T., Izumi, Y., Takada-Takatori, Y.
  • Organizer: XIII International Symposium on Cholinergic Mechanisms
  • Place of Presentation: Foz do Iguasu, Brazil
  • Year and Date: 2008-08-20
• [Presentation] Mechanisms of neuroprotective effects of nicotine and acetylcholinesterase inhibitors : role of alpha4 and alpha7 receptors in neuroprotection (2008)
  • Author(s): Akaike, A., Kume, T., Izumi, Y. and Takada-Takatori, Y.
  • Organizer: XIII International Symposium on Cholinergic Mechanisms
  • Place of Presentation: Foz do Iguasu, Brazil
  • Year and Date: 2008-08-20
• [Presentation] 培養アストロサイトのα7ニコチン受容体のニューロンとの相互作用による発現制御 (2008)
  • Author(s): 久米利明, 森本典子, 泉安彦, 赤池昭紀
  • Organizer: Neuroscience 2008 第31回日本神経科学大会 The 31st Annual Meeting of tha Japan Neuroscience Society
  • Place of Presentation: 東京都
  • Year and Date: 2008-07-09
• [Presentation] 培養アストロサイトのa7ニコチン受容体のニューセンとの相互作用による発現制御 (2008)
  • Author(s): 久米利明, 森本典子, 泉安彦, 赤池昭紀
  • Organizer: Neuroscience 2008第31回日本神経科学大会 The 31st Annual Meeting of tha Japan Neuroscience
  • Place of Presentation: 東京都
  • Year and Date: 2008-07-09
• [Presentation] Na^+/Ca^<2+> exchanger阻害薬によるPC12細胞におけるNGF誘発性神経突起伸長の抑制. (2008)
  • Author(s): 小田徹, 久米利明, 泉安彦, 赤池昭紀
  • Organizer: 第113回日本薬理学会近畿部会
  • Place of Presentation: 岡山
  • Year and Date: 2008-06-20
• [Presentation] Na^+/Ca^<2+> exchanger 阻害薬によるPC12細胞におけるNGF誘発性神経突起伸長の抑制 (2008)
  • Author(s): 小田徹, 久米利明, 泉安彦, 赤池昭紀
  • Organizer: 第113回日本薬理学会近畿部会
  • Place of Presentation: 岡山
  • Year and Date: 2008-06-20
• [Presentation] Heme oxygenase-1 is degraded by ubiquitin-proteasome system and related to neuroprotective role (2008)
  • Author(s): Yamamoto, N., Izumi, Y., Kato, F., Kume, T., Sawada, H., Akaike, A.
  • Organizer: The 4th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
  • Place of Presentation: Kyoto, Japan
  • Year and Date: 2008-04-24
• [Presentation] Heme oxygenase-1 is degraded by ubiquitin-proteasome system and related to neuroprotective role (2008)
  • Author(s): Yamamoto, N., Izumi, Y., Kato, F., Kume. T., Sawada, H. and
  • Organizer: The 4th Seoul-Kyoto-Osaka Joint Symposium on Pharmaceutical Sciences for Young Scientists
  • Place of Presentation: Kyoto,J apan
  • Year and Date: 2008-04-24
• [Presentation] 出血性脳障害におけるポリアミン類の関与 (2008)
  • Author(s): 高木美佳子, 香月博志, 藤本真二, 大西正俊, 久米利明, 赤池昭紀
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-28
• [Presentation] 酸化ストレスに対するイソチオシアネー卜類の神経保護作用機序 (2008)
  • Author(s): 水野景太, 久米利明, 武藤千恵, 泉安彦, 赤池昭紀
  • Organizer: 日本薬学会第128年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-27
• [Presentation] ユビキチン-プロテアソーム系のheme oxygenase-1の分解への寄与 : 神経保護作用との関係 (2008)
  • Author(s): 山本憲幸, 泉安彦, 加藤文彦, 久米利明, 澤田秀幸, 赤池昭紀
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-18
• [Presentation] ユビキチンープロテアソーム系のheme oxygenase-1の分解への寄与:神経保護作用との関係 (2008)
  • Author(s): 山本憲幸, 泉安彦, 加藤文彦, 久米利明, 澤田秀幸, 赤池昭紀
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-18
• [Presentation] 酸化ストレスに対するイソチオシアネート類の神経保護作用機序 (2008)
  • Author(s): 水野景太, 久米利明, 武藤千恵, 泉安彦, 赤池昭紀
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-17
• [Presentation] ドネペジル慢性処置した大脳皮質ニューロンにおける低濃度ドネペジル前処置の神経保護作用機序 (2008)
  • Author(s): 高鳥悠記, 久米利明, 大木雄太, 新留徹広, 藤井健志, 岡部進, 杉本八郎, 赤池昭紀
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-17
• [Presentation] グルタミン酸誘発ニューロン死に対するsulforaphaneの神経保護作用機序 (2008)
  • Author(s): 久米利明, 高田宜則, 水野景太, 赤池昭紀
  • Organizer: 第81回日本薬理学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2008-03-17
• [Presentation] イソチオシアネート類の中枢ニューロンにおける酸化的障害への有効性 (2007)
  • Author(s): 水野景太, 久米利明, 武藤千恵, 泉安彦, 赤池昭紀
  • Organizer: 第1回次世代を担う若手医療薬科学シンポジウム 医療を担う若手研究者の育成を目指して
  • Place of Presentation: 東京
  • Year and Date: 2007-12-16
• [Presentation] Heme oxygenase-1のユビキチン-プロテアソーム系による分解制御と神経保護効果 (2007)
  • Author(s): 山本憲幸, 泉安彦, 加藤文彦, 久米利明, 澤田秀幸, 赤池昭紀
  • Organizer: 第1回次世代を担う若手医療薬科学シンポジウム 医療を担う若手研究者の育成を目指して
  • Place of Presentation: 東京
  • Year and Date: 2007-12-16
• [Presentation] イソチオシアネート類の中枢ニューロンにおける酸化的障害への有効性 (2007)
  • Author(s): 水野景太, 久米利明, 武藤千恵, 泉安彦, 赤池昭紀
  • Organizer: 第1回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2007-12-16
• [Presentation] Heme oxygenase-1のユビキチンープロテアソーム系による分解制御と神経保護効果 (2007)
  • Author(s): 山本憲幸, 泉安彦, 加藤文彦, 久米利明, 澤田秀幸, 赤池昭紀
  • Organizer: 第1回次世代を担う若手医療薬科学シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2007-12-15
• [Presentation] PC12細胞におけるブロモクリプチンの神経突起伸長作用 (2007)
  • Author(s): 小田徹, 久米利明, 泉安彦, 赤池昭紀
  • Organizer: 第112回日本薬理学会近畿部会
  • Place of Presentation: 大阪
  • Year and Date: 2007-11-16
• [Presentation] グルタミン酸誘発ドパミンニューロン死における内在性ドパミンの関与 (2007)
  • Author(s): 泉安彦, 澤田秀幸, 山本憲幸, 久米利明, 香月博志,
  • Organizer: Neuro2007
  • Place of Presentation: 横浜
  • Year and Date: 2007-09-10
• [Presentation] 脱分極性刺激あるいは発火抑制による視床下部オレキシンニューロンの選択的消失 (2007)
  • Author(s): 黒須真介, 香月博志, 久米利明, 赤池昭紀
  • Organizer: 第111回日本薬理学会近畿部会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-06-15
• [Presentation] Cl-流入に依存した興奮毒性による網膜神経節細胞死 (2007)
  • Author(s): 浜康博, 香月博志, 角中ちひろ, 久米利明, 赤池昭紀
  • Organizer: 第111回日本薬理学会近畿部会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-06-15
• [Presentation] C1-流入に依存した興奮毒性による網膜神経節細胞死 (2007)
  • Author(s): 浜康博, 香月博志, 角中ちひろ, 久米利明, 赤池昭紀
  • Organizer: 第111回日本薬理学会近畿部会
  • Place of Presentation: 名古屋
  • Year and Date: 2007-06-15
• [Presentation] 培養大脳皮質ニューロンにおけるsulforaphaneの神経保護作用 (2007)
  • Author(s): 久米利明, 高田宜則, 水野景太, 香月博志, 赤池昭紀
  • Organizer: 日本ケミカルバイオロジー研究会 第2回年会
  • Place of Presentation: 京都
  • Year and Date: 2007-05-09