Research on the roles of metallothioneins in aging, brain ischemia and metabolic syndrome and drug discover

• Project/Area Number: 19390151
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Gifu University
• Principal Investigator: HOZUMI Isao Gifu University, 医学系研究科, 准教授 (20242430)
• Co-Investigator(Kenkyū-buntansha): INUZUKA Takashi 岐阜大学, 医学系研究科, 教授 (50184734) ; HAYASHI Yuichi 岐阜大学, 医学系研究科, 助教 (00392366) ; HARA Hideaki 岐阜薬科大, 薬学部, 教授 (20381717) ; SATOH Masahiko 愛知学院大学, 薬学部, 教授 (20256390) ; UCHIDA Yoko , 東京都高齢者研究所, 主任研究員 (60133633)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,980,000 (Direct Cost: ¥14,600,000、Indirect Cost: ¥4,380,000); Fiscal Year 2009: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2008: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2007: ¥12,740,000 (Direct Cost: ¥9,800,000、Indirect Cost: ¥2,940,000)
• Keywords: メタロチオネイン / 筋萎縮性側索硬化症 / 脳虚血 / 低分子化合物 / 神経成長抑制因子 / 運動 / 精神疾患 / 抗酸化作用 / 老化 / 味蕾 / メタボリック症候群 / アルツハイマー病 / 糖尿病

Research Abstract

メタロチオネイン-III(MT-III)は、メタロチオネイン-I/II(MT-I/II)同様、抗酸化作用、重金属解毒作用を有し、またMT-IIIは精神行動にも影響を与えていることを提示した。そして、MTs(MT-I/II, MT-IIIを総称)は血管障害、神経変性疾患、メタボリック症候群、精神疾患さらに老化と幅広い病態に関連していることを見出した。MTsまたその関連低分子化合物は特に筋萎縮性側索硬化症(ALS)、脳虚血の薬物治療薬としてきわめて有望なことを明らかにした。

Research Products

• [Journal Article] Microarray analysis of the liver in MT-III null mice treated with cadmium. (2010)
  • Author(s): Honda A, Komuro H, Nagase H, Hozumi I, Inuzuka T, Hara H, Fujiwara Y, Satoh M
  • Journal Title: J Toxicological Sciences 2 Pages: 271-273
  • Peer Reviewed
• [Journal Article] Resistance of metallothionein-III null mice to cadmium-induced acute hepatotoxicity. (2010)
  • Author(s): Honda A, Komuro H, Hasegawa T, Seko Y, Shimada A, Nagase H, Hozumi I, Inuzuka T, Hara H, Fujiwara Y, Satoh M
  • Journal Title: J Toxicological Sciences 2 Pages: 209-215
  • NAID: 10026193349
  • Peer Reviewed
• [Journal Article] Growth inhibitory factor inhibits the progression of amyotrophic lateral sclerosis. (2010)
  • Author(s): Hashimoto K, Hayashi Y, Inuzuka T, Hozumi I
  • Journal Title: Neurology 74 Suppl 2 A436
  • Peer Reviewed
• [Journal Article] Growth inhibitory factor inhibits the progression of amyotrophic lateral sclerosis (2010)
  • Author(s): Hashimoto K, Hayashi Y, Inuzuka T, Hozumi I
  • Journal Title: Neurology : A436. 2006 74 Suppl 2
  • Peer Reviewed
• [Journal Article] Resistance of metallothionein-III null mice to cadmium-induced acute hepatotoxicity (2010)
  • Author(s): Honda A, Komuro H, Hasegawa T, Seko Y, Shimada A, Nagase H, Hozumi I, Inuzuka T, Hara H, Fujiwara Y, SatohM
  • Journal Title: J Toxicological Sciences (in press)
  • NAID: 10026193349
  • Peer Reviewed
• [Journal Article] Microarray analysis of the liver in MT-III null mice treated with cad mium (2010)
  • Author(s): Honda A, Komuro H, Nagase H, Hozumi I, Inuzuka T, Hara H, Fujiwara Y, Satoh M
  • Journal Title: J Toxicological Sciences (in press)
  • Peer Reviewed
• [Journal Article] Metallothionein-3 deficient mice exhibit abnormalities of psychological behaviors. (2009)
  • Author(s): Koumura A, Kakefuda K, Honda A, Ito Y, Tsuruma K, Shimazawa M, Uchida Y, Hozumi I, Satoh M, Inuzuka T, Hara H
  • Journal Title: Neuroscience Letter 467 Pages: 11-14
  • Peer Reviewed
• [Journal Article] Metallothionein-III knockout mice aggravates the neuronal damage after transient focal cerebral ischemia. (2009)
  • Author(s): Koumura A, Hamanaka J, Shimazawa M, Honda A, Tsuruma K, Uchida Y, Hozumi I, Satoh M, Inuzuka T, Hara H
  • Journal Title: Brain Research 1292 Pages: 148-154
  • Peer Reviewed
• [Journal Article] DNA microarray of transcriptional responses of mouse spinal cords tophysical exercise. (2009)
  • Author(s): Hashimoto K, Honda A, Hayashi Y, Inuzuka T, Satoh M, Hozumi I
  • Journal Title: J Toxicological Sciences 34 Pages: 445-448
  • Peer Reviewed
• [Journal Article] Exercise induces metallothioneins in mouse spinal cord. (2009)
  • Author(s): Hashimoto K, Hayashi Y, Inuzuka T, Hozumi I
  • Journal Title: Neuroscience 163 Pages: 244-251
  • Peer Reviewed
• [Journal Article] Exercise induces metallothioneins in mouse spinal cord (2009)
  • Author(s): Hashimoto K, Hayashi Y, Inuzuka T, Hozumi I
  • Journal Title: Neuroscience 163 Pages: 244-251
  • Peer Reviewed
• [Journal Article] DNA microarray of transcriptional responses of mouse spinal cords to physical exercise (2009)
  • Author(s): Hashimoto K, Honda A, Hayashi Y, Inuzuka T, Satoh M, Hozumi I
  • Journal Title: J Toxicological Sciences 34 Pages: 445-448
  • Peer Reviewed
• [Journal Article] Metallothionein-III knockout mice aggravates the neuronal damage after transient focal cerebral ischemia (2009)
  • Author(s): Koumura A, Hamanaka J, Shimazawa M, Honda A, Tsuruma K, Uchida Y, Hozumi I, Satoh M, Inuzuka T, Hara H.
  • Journal Title: Brain Research 1292 Pages: 148-154
  • Peer Reviewed
• [Journal Article] Metallothionein-3 deficient mice exhibit abnormalities of psychological behaviors (2009)
  • Author(s): Koumura A, Kakefuda K, Honda A, Ito Y, Tsuruma K, Shimazawa M, Uchida Y, Hozumi I, Satoh M, Inuzuka T, Hara H
  • Journal Title: Neuroscience Letter 467 Pages: 11-14
  • Peer Reviewed
• [Journal Article] Metallothionein-3(GIF)is expressed in the brain and various peripheral organs of the rat. (2008)
  • Author(s): Hozumi I, Suzuki J S, Kanazawa H, Hara A, Saio M, Inuzuka T, Miyairi S, Naganuma A, Tohyama C
  • Journal Title: Neuroscience Letters 438 Pages: 54-58
  • Peer Reviewed
• [Journal Article] The expression of metallothionein is diminished in the spinal cords of patients with sporadic ALS. (2008)
  • Author(s): Hozumi I, Yamada M, Uchida Y, Ozawa K, Takahashi H, Inuzuka T
  • Journal Title: Amotrophic Lateral Sclerosis 9 Pages: 294-298
  • Peer Reviewed
• [Journal Article] Metallothionein-3 (GIF) is expressed in the brain and various peripheral organs of the rat. (2008)
  • Author(s): Hozumi I, Suzuki J S, Kanazawa H, Hara A, Saio M, Inuzuka T, Miyairi S, Naganuma A, Tohyama C.
  • Journal Title: Neuroscience Letters 438 Pages: 54-58
  • Peer Reviewed
• [Journal Article] The expression of metallothionein is diminished in the spinal cords of patients with sporadic ALS. (2008)
  • Author(s): Hozumi I, Yamada M, Uchida Y, Ozawa K, Takahashi H, Inuzuka T.
  • Journal Title: Amotrophic Lateral Sclerosis 9 Pages: 294-298
  • Peer Reviewed
• [Journal Article] 脳とメタロチオネイン -新展開するメタロチオネイン研究- (2008)
  • Author(s): 保住功
  • Journal Title: 医学のあゆみ 224 Pages: 300-301
• [Journal Article] The expression of metallothionein is diminished in the spinal cords of patients with sporadic ALS. (2008)
  • Author(s): Hozumi I, Yamada M, Uchida Y, Ozawa K, Takahashi H, Inuzuka T.
  • Journal Title: Amotrophic Lateral Sclerosis (印刷中)
  • Peer Reviewed
• [Journal Article] Metallothionein-3(GIF)is expressed in the brain and various peripheral organs of the rat. (2008)
  • Author(s): Hozumi I, Suzuki J S, Kanazawa H, Hara A, Saio M, Inuzuka T, Miyairi S, Naganuma A, Tohyama C.
  • Journal Title: Amotrophic Lateral Sclerosis (印刷中)
  • Peer Reviewed
• [Journal Article] Neuroprotective effect of erythropoietin and role of metallothionein-1 and-2 permanent focal cerebral ischemia. (2007)
  • Author(s): Wakida K, Shimazawa M, Hozumi I, Sato M, NagaseH, Inuzuka T, Hara H
  • Journal Title: Neuroscience 148 Pages: 105-114
  • Peer Reviewed
• [Journal Article] Neuroprotective effect of erythropoietin and role of metallothionein-1 and -2 permanent focal cerebral ischemia. (2007)
  • Author(s): Wakida K, Shimazawa M, Hozumi I, Sato M, NagaseH, Inuzuka T, Hara H.
  • Journal Title: Neuroscience 148 Pages: 105-114
  • Peer Reviewed
• [Presentation] Hozumi I Growth inhibitory factor inhibits the progression of amyotrophic lateral sclerosis (2010)
  • Author(s): Hashimoto K, Hayashi Y, Inuzuka T
  • Organizer: American Academy of Neurology
  • Place of Presentation: Toronto (Canada)
  • Year and Date: 2010-04-15
• [Presentation] 神経疾患におけるメタロチオネインの役割と治療への展望 (2009)
  • Author(s): 保住功
  • Organizer: 第6回岐阜脳科学研究会
  • Place of Presentation: アクティブG (岐阜市)
  • Year and Date: 2009-10-31
• [Presentation] 神経疾患におけるメタロチオネインの役割と治療への展望 (2009)
  • Author(s): 保住功
  • Organizer: 第6回岐阜腦科学研究会
  • Place of Presentation: アクティブG(岐阜市)
  • Year and Date: 2009-10-31
• [Presentation] 神経疾患におけるメタロチオネイン・重金属の役割と治療への展望 (2009)
  • Author(s): 保住功
  • Organizer: メタロチオネインおよびメタルバイオサイイエンス研究会
  • Place of Presentation: 東京大学山上会館(東京)
  • Year and Date: 2009-10-16
• [Presentation] 神経変性疾患患者における髄液重金属の測定 (2008)
  • Author(s): 保住功, 長谷川達也, 本田晶子, 佐藤雅彦, 林祐一, 山田恵, 桜井岳郎, 木村暁夫, 田中優司, 犬塚貴
  • Organizer: 第49回日本神経学会総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-05-16
• [Presentation] 神経変性疾患におけるメタロチオネインとメタルの役割 (2007)
  • Author(s): 保住功
  • Organizer: メタロチオネインおよびメタルバイオサイイエンス研究会
  • Place of Presentation: 徳島文理大国際会議場(徳島)
  • Year and Date: 2007-09-28
• [Presentation] 神経変性疾患におけるメタロチオネインとメタルの役割 (2007)
  • Author(s): 保住 功
  • Organizer: メタロチオネインおよびメタルバイオサイエンス研究
  • Place of Presentation: 徳島文理大学国際会議場
  • Year and Date: 2007-09-28
• [Book] 脳とメタロチオネイン-新展開するメタロチオネイン研究-(医学の歩み) (2008)
  • Author(s): 保住功