Molecular hydrogen control the disease state of nonalcoholic steatohepatitis and prevent cancer by modifying gene expression by influencing the epigenetic mechanism of histone methylation modification

• Project/Area Number: 26870682
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science; Eating habits
• Research Institution: Chubu University
• Principal Investigator: SOBUE Sayaka 中部大学, 臨床検査技術教育・実習センター, 講師 (50513347)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 水素 / 非アルコール性脂肪肝炎

Outline of Final Research Achievements

Nonalcoholic steatohepatitis (NASH) is one of lifestyle-related diseases drawing more attention in recent years and develops in patients with diabetes and/or dyslipidemia based on obesity. Molecular hydrogen has been shown to exhibit anti-inflammatory effect as well as an antioxidative effect. Therefore, we investigated whether the progression of liver cancer in NASH model mice can be suppressed by molecular hydrogen. We found that molecular hydrogen controls second hit of inflammation and oxidative stress leading to the onset of NASH, as well as protecting the mitochondria by modifying gene expression by influencing the epigenetic mechanism of histone methylation modification, simultaneously inducing mtUPR.

Research Products

• [Journal Article] Molecular hydrogen upregulates heat shock response and collagen biosynthesis, and downregulates cell cycles - Meta-analyses of gene expression profiles (2018)
  • Author(s): Hiroshi Nishiwak,i, Ito Mikako , Shuto Negishi, Sobue Sayaka, Ichihara Masatoshi, Ohno Kinji
  • Journal Title: Free Radic Res. Volume: - Issue: 4 Pages: 1-12
  • DOI: 10.1080/10715762.2018.1439166
  • Peer Reviewed
• [Journal Article] Molecular hydrogen modulates gene expression via histone modification and induces the mitochondrial unfolded protein response (2017)
  • Author(s): Sobue Sayaka、Inoue Chisato、Hori Fumiko、Qiao Shanlou、Murate Takashi、Ichihara Masatoshi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 493 Issue: 1 Pages: 318-324
  • DOI: 10.1016/j.bbrc.2017.09.024
  • Peer Reviewed
• [Journal Article] Modulation of the sphingolipid rheostat is involved in paclitaxel resistance of the human prostate cancer cell line PC3-PR (2016)
  • Author(s): Yuka Aoyama, Sayaka Sobue, Naoki Mizutani, Chisato Inoue, Yoshiyuki Kawamoto, Yuji Nishizawa, Masatoshi Ichihara, Mamoru Kyogashima, Motoshi Suzuki, Yoshinoti Nozawa, Takashi Murate
  • Journal Title: Biochem Biophys Res Commun Volume: 486 Issue: 2 Pages: 551-557
  • DOI: 10.1016/j.bbrc.2017.03.084
  • Peer Reviewed / Open Access
• [Journal Article] Mechanism of paclitaxel resistance in a human prostate cancer cell line, PC3-PR, and its sensitization by cabazitaxel (2016)
  • Author(s): Sobue S, Mizutani N, Aoyama Y, Kawamoto Y, Suzuki M, Nozawa Y, Ichihara M, Murate T
  • Journal Title: Biochem Biophys Res Commun Volume: 479 Issue: 4 Pages: 808-813
  • DOI: 10.1016/j.bbrc.2016.09.128
  • Peer Reviewed
• [Journal Article] Characterization of gene expression profiling of mouse tissues obtained during the postmortem interval (2016)
  • Author(s): Sobue S, Sakata K, Sekijima Y, Qiao S, Murate T, Ichihara M.
  • Journal Title: Exp Mol Pathol. Volume: 100 Issue: 3 Pages: 482-92
  • DOI: 10.1016/j.yexmp.2016.05.007
  • Peer Reviewed
• [Journal Article] Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells. (2016)
  • Author(s): Mizutani N, Omori Y, Kawamoto Y, Sobue S, Ichihara M, Suzuki M, Kyogashima M, Nakamura M, Tamiya-Koizumi K, Nozawa Y, Murate T.
  • Journal Title: Biochem Biophys Res Commun Volume: 470 Issue: 4 Pages: 851-856
  • DOI: 10.1016/j.bbrc.2016.01.134
  • Peer Reviewed
• [Journal Article] 分子状水素によるマウス肝臓における遺伝子発現変化の解析 (2016)
  • Author(s): 祖父江沙矢加、市原正智
  • Journal Title: 中部大学生命健康科学研究所紀要 Volume: 12 Pages: 38-41
  • NAID: 120006520501
  • Open Access
• [Journal Article] Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. (2015)
  • Author(s): Ichihara M, Sobue S, Ito M, Ito M, Hirayama M, Ohno K.
  • Journal Title: Med Gas Res Volume: 5 Issue: 1 Pages: 12-12
  • DOI: 10.1186/s13618-015-0035-1
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Simultaneous oral and inhalational intake of molecular hydrogen additively suppresses signaling pathways in rodents. (2015)
  • Author(s): Sobue S, Yamai K, Ito M, Ohno K, Ito M, Iwamoto T, Qiao S, Ohkuwa T, Ichihara M.
  • Journal Title: Mol Cell Biochem. Volume: 403 Pages: 231-241
  • Peer Reviewed
• [Journal Article] Photoshopを用いた画像解析の検討 (2014)
  • Author(s): 岩田晃裕、土本詩織、市原正智、祖父江沙矢加
  • Journal Title: 社団法人 愛知県臨床衛生検査技師会誌 らぼ Volume: 65 Pages: 11-14
• [Journal Article] UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factor α and interleukin 6. (2014)
  • Author(s): Miyata M.
  • Journal Title: Biochem Biophys Res Commun. Volume: 445 Issue: 2 Pages: 504-10
  • DOI: 10.1016/j.bbrc.2014.02.038
  • Peer Reviewed / Open Access
• [Journal Article] Detection of a Soluble Form of CD109 in Serum of CD109 Transgenic and Tumor Xenografted Mice. (2014)
  • Author(s): Sakakura H, Murakumo Y, Mii S, Hagiwara S, Kato T, Asai M, Hoshino A, Yamamoto N, Sobue S, Ichihara M, Ueda M, Takahashi M.
  • Journal Title: PLoS One Volume: 9 Issue: 1 Pages: e83385-e83385
  • DOI: 10.1371/journal.pone.0083385
  • Peer Reviewed
• [Presentation] 分子状水素はH3K27のメチル化状態を変化させ遺伝子発現を修飾しmtUPRを誘導する (2017)
  • Author(s): 祖父江沙矢加、井上千聖、堀文子、村手隆、市原正智
  • Organizer: 第40回日本分子生物学会年会
• [Presentation] 分子状水素はエピジェネティックに遺伝子発現を修飾するとともにmtUPRを誘導し生体を保護する (2017)
  • Author(s): 祖父江沙矢加、井上千聖、堀文子、西沢祐治、村手隆、市原正智
  • Organizer: 第7 回日本分子状水素医学生物学会大会
• [Presentation] Molecular hydrogen activates the mitochondrial unfolded protein response via epigenetic histone modification and ameliorates ultraviolet light-induced damage in Caenorhabditis elegans (2017)
  • Author(s): Sayaka Sobue, Chisato Inoue, Fumiko Hori, Takashi Murate, Masatoshi Ichihara
  • Organizer: 8th World Congress on Targeting Mitochondria 2017
  • Int'l Joint Research
• [Presentation] 水素による紫外線障害軽減効果の線虫を用いた分子機構の解明 (2016)
  • Author(s): 井上千聖、祖父江沙矢加、長谷川浩一、堀文子、市原正智
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2016-11-30
• [Presentation] 分子状水素による肝障害軽減作用の背景にあるミトコンドリア保護効果に関与する分子機構の解析 (2016)
  • Author(s): 祖父江沙矢加、岡本陽、安形則雄、市原正智
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター
  • Year and Date: 2016-09-25
• [Presentation] Development of effective method for preventing life environment factor-induced diseases using molecular hydrogen. (2015)
  • Author(s): Sobue S, Ichihara M.
  • Organizer: ICITE for SD-2015
  • Place of Presentation: Chubu University (Kasugai)
  • Year and Date: 2015-11-07
  • Int'l Joint Research
• [Presentation] Molecular hydrogen is a novel antioxidant to reduce oxidative stress and attenuate disease progression through modification of cell signaling and gene expressions. (2015)
  • Author(s): Sobue S, Inoue C, Hori F, Ito M, Ohno K, Ichihara M.
  • Organizer: 15th International Conference on Oxidative Stress Reduction, Redox Homeostasis &Antioxidants
  • Place of Presentation: Paris (France)
  • Year and Date: 2015-06-24
  • Int'l Joint Research
• [Presentation] 水素ガスおよび水素水の併用投与が細胞内シグナル伝達に与える影響の検討 (2015)
  • Author(s): 祖父江沙矢加、井上千聖、伊藤美佳子、大野欽司、伊藤雅史、市原正智
  • Organizer: 第5回分子状水素医学シンポジウム
  • Place of Presentation: ウインクあいち（愛知県・名古屋市）
  • Year and Date: 2015-03-21
• [Presentation] UVB照射ケラチノサイトは炎症性サイトカインを分泌してメラノサイトにおける癌関連GD3合成酵素遺伝子の発現を誘導する (2014)
  • Author(s): 古川圭子、宮田麻衣子、田島織絵、神戸真理子、市原正智、祖父江沙矢加、古川鋼一
  • Organizer: 第73回日本癌学会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] 当院における血管内大細胞型B細胞性リンパ腫の特徴 (2014)
  • Author(s): 祖父江沙矢加、新川和功、三田村桂二、杉山直久、加納彩野、市川沙絵子、小杉浩史、岩田洋介、市原正智
  • Organizer: 第15回日本検査血液学会学術集会
  • Place of Presentation: 仙台国際センター（宮城県・仙台市）
  • Year and Date: 2014-07-21
• [Presentation] UVB-irradiated keratinocytes induce melanoma-associated ganglioside GD3 synthase gene in melanocytes via secretion of tumor necrosis factorα and interleukin 6 (2014)
  • Author(s): Keiko Furukawa, Maiko Miyata, Masatoshi Ichihara, Orie Tajima, Sayaka Sobue, Mariko Kambe, Kazumitsu Sugiura, Koichi Furukawa
  • Organizer: 9th International Symposium Glycosyltransferase
  • Place of Presentation: Porto, Portugal
  • Year and Date: 2014-06-18 – 2014-06-21