Prevention of neuronal cell death associated with altered redox in the endoplasmic reticulum(ER)

• Project/Area Number: 19500319
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kanazawa University
• Principal Investigator: HORI Osamu Kanazawa University, 医学系, 准教授 (60303947)
• Co-Investigator(Kenkyū-buntansha): OGAWA Satoshi 金沢大学, 医学系, 教授 (90283746) ; KITAO Yasuko 金沢大学, 医学系, 助教 (00019613)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2007: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 神経科学 / 脳神経疾患 / ストレス / 神経細胞死

Research Abstract

神経系細胞株PC12をBSOで処理すると、(1)細胞内グルタチオンの枯渇、(2)小胞体内での酸化ストレス発生、そして(3)細胞死が誘導された。この時、細胞を小胞体ストレス誘導剤ツニカマイシンで処理すると細胞死は増加し、逆に小胞体ストレス制御物質で処理すると減少した。マウスパーキンソン病(PD)モデルにおいても、(1)細胞内グルタチオンの低下、(2)小胞体ストレスの増加、(3)神経細胞死が認められた事から、グルタチオン枯渇により誘導される小胞体ストレス由来神経細胞死の重要性が示唆された。

Research Products

• [Journal Article] A Carbazole derivative protects cells against endoplasmic reticulum(ER)stress and glutathione depletion (2008)
  • Author(s): Miura H, Takano K, Kitao Y, Hibino S, Choshi T, Murakami R, Suzuki H, Yamada M, Ogawa S, Hori O
  • Journal Title: J Pharma Sci 108 Pages: 164-71
  • NAID: 10024384874
  • Peer Reviewed
• [Journal Article] Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction (2008)
  • Author(s): Stanyer L, Jorgensen W, Hori O, Clark JB, Heales SJ
  • Journal Title: Neurochem Int 53(3-4) Pages: 95-101
  • Peer Reviewed
• [Journal Article] Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction. (2008)
  • Author(s): Stanyer L, et al.
  • Journal Title: Neurochem Int. 53(3-4) Pages: 95-101
  • Peer Reviewed
• [Journal Article] A Carbazole Derivative Protects Cells Against Endoplasmic Reticulum (ER) Stress and Glutathione Depletion. (2008)
  • Author(s): Miura H, et al.
  • Journal Title: J Pharmacol Sci. 108(2 Pages: 164-171
  • Peer Reviewed
• [Journal Article] A DIBENZOYLMETHANE(DBM)DERIVATIV PROTECTS DOPAMINERGIC NEURONS AGAINST BOTH OXIDATIVE STRESS AND ENDOPLAMIC RETICULUM(ER)STRESS (2007)
  • Author(s): Takano K, Kitao Y, Tabata Y, Miura H, Sato K, Takuma K, Yamada K, Hibino S, Choshi T, Iinuma M, Suzuki H, Murakami R, Yamada M, Ogawa S, Hori O
  • Journal Title: Am J Physiol cell Physiol 293(6) Pages: 1884-94
  • Peer Reviewed
• [Journal Article] A novel inhibitor of advanced glycation and endoplasmic reticulum stress reduces infarct volume in rat focal cerebral ischemia (2007)
  • Author(s): Miyata T, Takizawa S, Izuhara Y, Kitao Y, Hori O, Ogawa S, Morita Y, Takagi S, Strihou CY
  • Journal Title: Brain Res 1183 Pages: 124-37
  • Peer Reviewed
• [Journal Article] a resveratrol tetramer, regulates endoplasmic reticulum(ER)stress and inflammation (2007)
  • Author(s): Tabata Y, Takano K, Ito T, Iinuma M, Yoshimoto T, Miura H, Kitao Y, Ogawa S, Hori O. Vaticanol B
  • Journal Title: Am J Physiol Cell Physiol 293(1)
  • Peer Reviewed
• [Journal Article] Ischemia-induced neuronal cell death and stress response (2007)
  • Author(s): Ogawa S, Kitao Y, Hori O
  • Journal Title: Antioxid Redox Signal 9(5) Pages: 573-87
  • Peer Reviewed
• [Journal Article] Hypoxia-mediated induction of heme oxygenase type I and carbon monoxide release from astrocytes protects nearby cerebral neurons from hypoxia-mediated apoptosis (2007)
  • Author(s): Imuta N, Hori O, Kitao Y, Tabata Y, Yoshimoto T, Matsuyama T, Ogawa S
  • Journal Title: Antioxid Redox Signal 9(5) Pages: 543-52
  • Peer Reviewed
• [Journal Article] Does ORP150/HSP12A protect dopaminergic neurons against MPTP/MPP(+)-induced neurotoxicity? (2007)
  • Author(s): Kitao Y, Matsuyama T, Takano K, Tabata Y, Yoshimoto T, Momoi T, Yamatodani A, Ogawa S, Hori O
  • Journal Title: Antioxid Redox Signal 9(5) Pages: 589-95
  • Peer Reviewed
• [Journal Article] Pael receptor induces death of dopaminergic neurons in the substantia nigra via endoplasmic reticulum stress and dopamine t oxicity, which is enhanced under condition of parkin inactivation (2007)
  • Author(s): Kitao Y, Imai Y, Ozawa K, Kataoka A, Ikeda T, Soda M, Nakimawa K, Kiyama H, Stern DM, Hori O, Wakamatsu K, Ito S, Itohara S, Takahashi R, Ogawa S
  • Journal Title: Hum Mol Genet 16(1) Pages: 50-60
  • Peer Reviewed
• [Journal Article] Methoxyflavones protect cells against endoplasmic reticulum(ER)stress and neurotoxin (2007)
  • Author(s): Takano K, Tabata Y, Kitao Y, Murakami R, Suzuki H, Yamada M, Iinuma M, Yoneda Y, Ogawa S, Hori O
  • Journal Title: Am J. Physiol(Cell Physiol) 292(1)
  • NAID: 40015637308
  • Peer Reviewed
• [Journal Article] Methoxyflavones protect cells against endoplasmic reticulum (ER) stress and neurotoxin (2007)
  • Author(s): Takano K, et. al.
  • Journal Title: Am. J. Physiol. Cell Physiol. 292(1) Pages: 353-361
  • Peer Reviewed
• [Journal Article] Vaticanol B, a resveratrol tetramer, regulates endoplasmic reticulum (E'R) stress and inflammation (2007)
  • Author(s): Tabata Y, et. al.
  • Journal Title: Am. J. Physiol. Cell Physiol. 293(1) Pages: 411-418
  • Peer Reviewed
• [Journal Article] A dibenzoylmethane (DBM) derivative protects dopaminergic neurons against both oxidative stress and endoplamic reticulum (ER) stress. (2007)
  • Author(s): Takano K, et. al.
  • Journal Title: Am. J. Physiol. Cell Physiol.\ 293(6) Pages: 1884-1894
  • Peer Reviewed
• [Journal Article] Pael receptor induces death of dopaminergic neurons in the substantianigra via endoplasmic reticulum stress and dopamine toxicity, which is enhanced under condition of parkin inactivation. (2007)
  • Author(s): Kitao Y, et. al.
  • Journal Title: Human Mol. Genetics. 16(1) Pages: 50-60
  • Peer Reviewed
• [Journal Article] Hypoxia-mediated induction of heme oxygenase type I and carbon monoxide release from astrocytes protects nearby cerebral neurons from hypoxia-mediated apoptosis. (2007)
  • Author(s): Imuta N, et. al.
  • Journal Title: Antioxid Redox Signal. 9 Pages: 573-587
  • Peer Reviewed
• [Journal Article] Ischemia-induced neuronal cell death and stress response. (2007)
  • Author(s): Ogawa S, et. al.
  • Journal Title: Antioxid Redox Signal. 9 Pages: 1884-1894
  • Peer Reviewed
• [Journal Article] Does ORP150/HSP12A protect dopaminergic neurons against MPTP/MPP(+)-induced neurotoxicity? (2007)
  • Author(s): Kitao Y, et. al.
  • Journal Title: Antioxid Redox Signal 9 Pages: 589-595
  • Peer Reviewed
• [Journal Article] A novel inhibitor of advanced glycation and endoplasmic reticulum stress reduces infarct volume in rat focal cerebral ischemia. (2007)
  • Author(s): Miyata T, et. al.
  • Journal Title: Brain Res. 1183 Pages: 124-37
  • Peer Reviewed
• [Presentation] A Carbazole derivative protects cells against ehdoplasmic reticulum (ER) stress and glutathione depletion (2008)
  • Author(s): Awa, et al.
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Decreased expression of ERAD molecule Herp facilitates degradation of α-synuclein and synphilin-1 (2008)
  • Author(s): Hashida, et al.
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] NDRG2 regulates the motility of astroglial cells (2008)
  • Author(s): Takeichi, et al.
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] Decreased expression of ERAD molecule Herp facilitates degradation of a-synuclein and synphilin-1 (2008)
  • Author(s): 三浦 比佳理, 他
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
  • Year and Date: 2008-07-09
• [Presentation] ER stress response and neuronal cell death in the substantia nigra (2008)
  • Author(s): Hori O
  • Organizer: 日本神経化学会
  • Place of Presentation: 富山
  • Year and Date: 2008-03-13
• [Presentation] NDRG2 regulates the motility of astroglial cells (2008)
  • Author(s): Takeichi T, Kitao Y, Miura H, Kitamura O, Ogawa S, Hori O
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会合同大会
  • Place of Presentation: 神戸
• [Presentation] A Carbazole derivative protects cells against endoplasmic reticulum(ER)stress and glutathione depletion (2008)
  • Author(s): Awa Y, Miura H, Hashida K, Kitao Y, Hibino S, Choshi T, Murakami R, Suzuki H, Yamada M, Ogawa S and Hori O
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会合同大会
  • Place of Presentation: 神戸
• [Presentation] Decreased expression of ERAD molecule Herp facilitates degradation of α-synuclein and synphilin-1 (2008)
  • Author(s): Hashida K, Miura H, Awa Y, Ogawa S, Kitao Y, and Hori O
  • Organizer: 第31回日本分子生物学会年会、第81回日本生化学会合同大会
  • Place of Presentation: 神戸
• [Presentation] Decreased expression of ERAD molecule Herp facilitates degradation of α-synuclein and synphilin-1 (2008)
  • Author(s): Miura H, Kitao Y, Ogawa S and Hori O
  • Organizer: The 31st annual meeting of the Japan Neuroscience Society
  • Place of Presentation: 東京
• [Presentation] a resveratol tetramer, regulates endoplasmic reticulum(ER)stress and inflammation (2007)
  • Author(s): Miura H, Kitao Y、Ogawa S、Hori O. Vaticanol B
  • Organizer: 第30回日本分子生物学会年会、第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] Vaticanol B, a resveratrol tetramer,regulates endoplasmic reticulum (ER)stress and inflammation (2007)
  • Author(s): Miura H, et. al.
  • Organizer: 第30回日本分子生物学会年会、第80回日本生化学会大会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-11
• [Presentation] A screening system for compounds to protect cells against endoplasmic reticulum(ER)stress (2007)
  • Author(s): Hori O
  • Organizer: 6th World Congress on Alternatives and Animal Use in the Life Science(Japanese Society for Alternatives and Animal Experiments)
  • Place of Presentation: Tokyo
  • Year and Date: 2007-08-25
• [Presentation] A screening system for compounds to protect cells against endoplasmic reticulum (ER) stress (2007)
  • Author(s): Hori O
  • Organizer: 第6回動物実験代替法世界大会
  • Place of Presentation: 東京
  • Year and Date: 2007-08-25
• [Patent(Industrial Property Rights)] ピリミジン誘導剤を有効成分とする医薬組成物 (2009)
  • Inventor(s): 堀修, 他
  • Industrial Property Rights Holder: 金沢大学・明治乳業
  • Industrial Property Number: 2007-306399
  • Filing Date: 2009-11-27
• [Patent(Industrial Property Rights)] 小胞体ストレス制御化合物とそれを有効成分とする医薬組成物 (2009)
  • Inventor(s): 堀修, 他
  • Industrial Property Rights Holder: 金沢大学・明治乳業
  • Filing Date: 2009-05-25
  • Overseas
• [Patent(Industrial Property Rights)] 小胞体ストレス制御物質とそれを有効成分とする医薬組成物 (2007)
  • Inventor(s): 堀 修, 他
  • Industrial Property Rights Holder: 明治乳業
  • Filing Date: 2007-05-25
  • Overseas
• [Patent(Industrial Property Rights)] ピリミジン誘導剤を有効成分とする医薬組成物 (2007)
  • Inventor(s): 堀 修, 他
  • Industrial Property Rights Holder: 金沢大学明治乳業
  • Filing Date: 2007-11-27