Screening of novel molecules that regulate the histone deacetylase activity from foods and development of nerve regeneration treatment

• Project/Area Number: 25750059
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Eating habits
• Research Institution: Yamanashi Gakuin University
• Principal Investigator: NATORI Takamitsu 山梨学院大学, 健康栄養学部, 准教授 (00528721)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: HDAC / アントシアニジン / 神経保護効果 / 神経突起伸長 / ヒストンアセチル化 / ｐ53 / Hdac / p53 / ヒストン脱アセチル化酵素 / 神経突起伸長効果 / ポリフェノール類 / 脊髄損傷

Outline of Final Research Achievements

We found that cyanidin and peonidin inhibited histone deacetylase (HDAC) and increased histone acetylation. Using a primary culture neuronal cells and SH-SY5Y cell lines to consider the effect on the neuronal cell protective effect and the neurite outgrowth. Cyanidin and peonidin protected SH-SY5Y cells from endoplasmic reticulum stress, and promoted neuronal outgrowth in primary cultured neuronal cells. Cyanidin and peonidin decreased CHOP expression and increased GAP-43 expression. On the other hand acetylated p53 localized to the nucleus. Our data suggests that the neuroprotection and neurite elongation by cyanidin and peonidin might be involved in acetylation of histone and p53.

Research Products

• [Journal Article] Induction of apoptosis by extracts of edible wild plants in C6 glioma cells. (2015)
  • Author(s): 名取貴光・中川裕子・桜林ひかる・福井智・野田聖子・窪島愛華・戸澤一宏・仲尾玲子
  • Journal Title: 日本食品保蔵科学会 Volume: 41（3） Pages: 88-91
  • NAID: 40020503537
  • Peer Reviewed
• [Journal Article] Keratan sulfate expression in microglia is diminished in the spinal cord in experimental autoimmune neuritis. (2013)
  • Author(s): Matsui H, Ohgomori T, Natori T, Miyamoto K, Kusunoki S, Sakamoto K, Ishiguro N, Imagama S, Kadomatsu K.
  • Journal Title: Cell Death Dis. Volume: 4
  • Peer Reviewed
• [Journal Article] Ablation of Keratan Sulfate Accelerates Early Phase Pathogenesis of ALS. (2013)
  • Author(s): Hirano K, Ohgomori T, Kobayashi K, Tanaka F, Matsumoto T, Natori T, Matsuyama Y, Uchimura K, Sakamoto K, Takeuchi H, Hirakawa A, Suzumura A, Sobue G, Ishiguro N, Imagama S, Kadomatsu K.
  • Journal Title: PLoS One Volume: 8
  • NAID: 120005946841
  • Peer Reviewed
• [Journal Article] Midkine overcomes neurite outgrowth inhibition of chondroitin sulfate proteoglycan without glial activation and promotes functional recovery after spinal cord injury. (2013)
  • Author(s): Muramoto A, Imagama S, Natori T, Wakao N, Ando K, Tauchi R, Hirano K, Shinjo R, Matsumoto T, Ishiguro N, Kadomatsu K.
  • Journal Title: Neuroscience letters Volume: 550 Pages: 150-155
  • Peer Reviewed
• [Presentation] 在来農産物によるアミロイドβ凝集抑制および神経細胞保護効果について (2015)
  • Author(s): 名取貴光
  • Organizer: 日本食品保蔵科学会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-28
• [Presentation] モモ果実の機能性評価と加工食品（ギモーブ）の開発 (2015)
  • Author(s): 小田切香、名取貴光、仲尾玲子
  • Organizer: 日本食品保蔵科学会
  • Place of Presentation: 東京
  • Year and Date: 2015-06-28
• [Presentation] Keratan sulfate regulate neuronal plasticity in visual cortex. (2014)
  • Author(s): T. Natori, K. Nagai, Y. Komatsu, K. Kadomatsu.
  • Organizer: 44th Annual meeting of the Society for Neuroscience.
  • Place of Presentation: Washington, DC（米国）
  • Year and Date: 2014-11-16
• [Presentation] Phytanic acid induces Neuro2a cell death via histone deacetylase activation (2014)
  • Author(s): K. Nagai, T. Natori.
  • Organizer: 44th Annual meeting of the Society for Neuroscience.
  • Place of Presentation: Washington, DC（米国）
  • Year and Date: 2014-11-16
• [Presentation] アントシアニンのヒストン脱アセチル化を介した神経細胞保護及び神経突起伸長作用 (2014)
  • Author(s): 名取貴光、長井薫
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都府）
  • Year and Date: 2014-10-18
• [Presentation] フィタン酸はヒストン脱アセチル化酵素(Hdac)活性化とミトコンドリア障害を介しNeuro2a細胞に細胞死を誘導する (2014)
  • Author(s): 長井薫、名取貴光
  • Organizer: 第87回日本生化学会大会
  • Place of Presentation: 国立京都国際会館（京都府）
  • Year and Date: 2014-10-18
• [Presentation] 天然色素による神経突起伸長および神経保護効果について (2014)
  • Author(s): 名取貴光、中川裕子、仲尾玲子
  • Organizer: 日本食品保蔵科学 第63回大会
  • Place of Presentation: JA長野県ビル（長野県）
  • Year and Date: 2014-06-28
• [Presentation] 植物性食品由来抽出物に含まれる機能性成分の網羅的解析 (2014)
  • Author(s): 仲尾玲子、小田切 香、吉原沙奈恵、中川裕子、名取貴光
  • Organizer: 日本食品保蔵科学 第63回大会
  • Place of Presentation: JA長野県ビル（長野県）
  • Year and Date: 2014-06-28
• [Presentation] Neurite outgrowth and neuroprotective effect by polyphenols is regulated by histone deacetylase (HDAC) families. (2014)
  • Author(s): 名取貴光、長井薫
  • Organizer: 日本農芸化学会
  • Place of Presentation: 東京
• [Presentation] 山菜ポリフェノールの抗酸化活性とヒストン脱アセチル化酵素（HDAC）の活性調節について (2013)
  • Author(s): 杉山茜、望月春菜、名取貴光、中川裕子、仲尾玲子
  • Organizer: 日本食品保蔵科学会
  • Place of Presentation: 山形
• [Presentation] Ablation of Keratan Sulfate accelerates early pathogenesis of ALS. (2013)
  • Author(s): 大篭友博、平野健一、小林和克、松本智宏、名取貴光、平川晃弘、今釜史郎、門松健治
  • Organizer: 日本神経科学会
  • Place of Presentation: 京都
• [Presentation] Relationship of histone deacetylation and natural product-derived pigments exhibit anti-inflammatory activity and neuroprotective effects. (2013)
  • Author(s): 名取貴光 長井薫
  • Organizer: 日本生化学会
  • Place of Presentation: 横浜
• [Book] 新・野菜の便利帳 (2016)
  • Author(s): 名取貴光
  • Total Pages: 176
  • Publisher: 高橋書店
• [Book] 基礎化学と生命化学 (2014)
  • Author(s): 吉田真史、谷口亜樹子、名取貴光、大道公秀、茂木秀喜、成井浩二
  • Total Pages: 162
  • Publisher: 光生館