Functional analysis of histone deacetylase SIRT in the pathophysiology of neurodegenerative disorders

• Project/Area Number: 21591096
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Sapporo Medical University
• Principal Investigator: HISAHARA Shin 札幌医科大学, 医学部, 助教 (80336403)
• Co-Investigator(Kenkyū-buntansha): SHIMOHAMA Shun 札幌医科大学, 医学部, 教授 (60235687)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 神経分子病態学 / ヒストン脱アセチル化酵素 / SIRTファミリー / パーキンソン病 / 酸化ストレス / 細胞死

Research Abstract

We now have investigating the function of histone deacetylase SIRT(sirtuin). To explore preventive effect against cell death, we have performed cell viability assay in PC12 and SHSY5Y cells with administration of hydrogen peroxide(H2O2) and 6-hydroxydopamine(6-OHDA). Administration of resveratrol, an activator of SIRT, and overexpression of SIRT1 resulted in significant inhibition of oxidative stress-induced cell death. We also found that overexpression of SIRT1H355Y, a dominant-negative SIRT1, showed partial inhibition of cell death. These results indicate that SIRT1 promotes cellular viability via deacetylase activity-dependent and -independent mechanisms.

Research Products

• [Journal Article] Dopamine Receptors and Parkinson's Disease (2011)
  • Author(s): Shin Hisahara and Shun Shimohama
  • Journal Title: International Journal of Medicinal Chemistry
  • Peer Reviewed
• [Journal Article] Toxin-Induced and Genetic Animal Models of Parkinson's Disease (2011)
  • Author(s): Shin Hisahara and Shun Shimohama
  • Journal Title: Parkinson's Disease
  • Peer Reviewed
• [Journal Article] Relationship between dysphagia and depressive states in patients with Parkinson's disease (2011)
  • Author(s): Meng Han, Hirofumi Ohnishi, Michio Nonaka, Rika Yamauchi, Takayoshi Hozuki, Takashi Hayashi, Masaki Saitoh, Shin Hisahara, Tomihiro Imai, Shun Shimohama, Mitsuru Mori
  • Journal Title: Parkinson's Disease & Related Disorders Volume: 17 Pages: 437-439
  • Peer Reviewed
• [Journal Article] Dopamine Receptors and Parkinson's Disease (2011)
  • Author(s): Shin Hisahara, Shun Shimohama
  • Journal Title: International Journal of Medicinal Chemistry Volume: 2011 Pages: 1-16
  • DOI: 10.1155/2011/403039
  • Peer Reviewed
• [Journal Article] Toxin-Induced and Genetic Animal Models of Parkinson's Disease (2011)
  • Author(s): Shin Hisahara, Shun Shimohama
  • Journal Title: Parkinson's Disease Volume: 2011 Pages: 951709-951709
  • Peer Reviewed
• [Journal Article] Relationship between dysphagia and depressive states in patients with Parkinson's disease (2011)
  • Author(s): Meng Han, Hirofumi Ohnishi, Michio Nonaka, Rika Yamauchi, Takayoshi Hozuki, Takashi Hayashi, Masaki Saitoh, Shin Hisehara, Tomihiro Imai, Shun Shimohama, Mitsuru Mori
  • Journal Title: Parkinson's Disease & Related Disorders Volume: (In press)
  • Peer Reviewed
• [Journal Article] Response of serum carboxylated and undercarboxylated osteocalcin to risedronate monotherapy and combined therapy with vitamin K(2) in corticosteroid-treated patients : a pilot study (2010)
  • Author(s): Hozuki T, Imai T, Tsuda E, Matsumura A, Yamamoto D, Toyoshima T, Suzuki S, Yamauchi R, Hayashi T, Hisahara S, Shimohama S
  • Journal Title: Intern Med Volume: 49 Pages: 371-6
  • NAID: 130000251679
  • Peer Reviewed
• [Journal Article] Correlation of bite force with excitation-contraction coupling time of the masseter in myasthenia gravis (2010)
  • Author(s): Tsuda E, Imai T, Hozuki T, Yamauchi R, Saitoh M, Hisahara S, Yoshikawa H, Motomur M, Shimohama S
  • Journal Title: Clin Neurophysiol Volume: 121 Pages: 1051-8
  • Peer Reviewed
• [Journal Article] Induction of manganese superoxide dismutase by nuclear translocation and activation of SIRT1 promotes cell survival in chronic heart failure (2010)
  • Author(s): Tanno M, Kuno A, Yano T, Miura T, Hisahara S, Ishikawa S, Shimamoto K and Horio Y
  • Journal Title: J. Biol. Chem Volume: 285 Pages: 8375-8382
  • Peer Reviewed
• [Presentation] Resver atrolによる神経系細胞における酸化ストレス耐性の検討 (2010)
  • Author(s): 久原真、堀尾嘉幸、下濱俊
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-22
• [Presentation] Resveratrolによる神経系細胞における酸化ストレス耐性の検討 (2010)
  • Author(s): 久原真、堀尾嘉幸、下濱俊
  • Organizer: 第51回日本神経学会総会
  • Place of Presentation: 東京
  • Year and Date: 2010-05-22
• [Presentation] Histone deacetylase SIRT1 modulates neuronal differentiation (2009)
  • Author(s): S. Hisahara, M. Tanno, S. Shimohama, M. Sato, Y. Horio
  • Organizer: Annual Meeting of Society for Neuroscience
  • Place of Presentation: アメリカ合衆国・シカゴ
  • Year and Date: 2009-10-20
• [Presentation] 培養神経幹細胞における分化特性とヒストン脱アセチル化酵素SIRT1の関与 (2009)
  • Author(s): 久原真、堀尾嘉幸、下濱俊
  • Organizer: 第50回日本神経学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2009-05-20
• [Book] Animal Models of Parkinson's Disease Induced by Toxins and Genetic Manipulation (2012)
  • Author(s): Shin Hisahara, Shun Shimohama
  • Publisher: In Tech
• [Book] Mechanisms in Parkinson's Disease-Models and Treatments (2011)
  • Author(s): Shin Hisahara and Shun Shimohama
  • Total Pages: 28
  • Publisher: InTech