Neuroprotective effect of H2 and in vivo redox state recording system of oxidative stress

• Project/Area Number: 24500871
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Nippon Medical School
• Principal Investigator: YOKOTA TAKASHI 日本医科大学, 付置研究所, その他 (30445829)
• Co-Investigator(Kenkyū-buntansha): OHTA Shigeo 日本医科大学, 大学院医学研究科, 教授 (00125832)
• Co-Investigator(Renkei-kenkyūsha): WOLF Alexsander 日本医科大学, 先端医学研究所細胞生物学部門, 講師 (20434136)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 水素分子 / 酸化ストレス / 抗酸化 / 水素 / 緑内障 / 抗酸化剤

Outline of Final Research Achievements

Oxidative and nitrative processes have an important role in the pathogenesis of glaucomatous neurodegeneration. Ｅxposure　of a nitric oxide donor, S-nitroso-N-acetylpenicillamine (SNAP) induce neuronal damage independently of peroxynitrite. We cultured rat retinal tissues in an organotypic culture system with SNAP, in the presence or absence of Molecular hydrogen　(H2). H2 suppressed loss of mitochondrial membrane potential and apoptosis in retinal cells. Moreover, H2 decreased the tyrosine nitration level and suppressed oxidative stress damage in retinal cells. SNAP treatment decreased the cell numbers in the retinal cell layer, but the presence of H2 inhibited this reduction. These findings suggest that H2 has a neuroprotective effect against retinal cell oxidative damage, presumably by scavenging peroxynitrite.
Thus, H2 may be an effective and novel clinical tool for treating glaucoma and other oxidative stress-related diseases.

Research Products

• [Journal Article] Intravenous transplantation of bone marrow-derived mononuclear cells prevents memory impairment in transgenic mouse models of Alzheimer's disease. (2015)
  • Author(s): Kanamaru T, Kamimura N, Yokota T, Nishimaki K, Iuchi K, Lee H, Takami S, Akashiba H, Shitaka Y, Ueda M, Katsura K, Kimura K, Ohta S.
  • Journal Title: Brain Res. Volume: 24
  • Peer Reviewed / Open Access
• [Journal Article] Oxidative stress accelerates amyloid deposition and memory impairment in a double-transgenic mouse model of Alzheimer's disease. (2015)
  • Author(s): Kanamaru T, Kamimura N, Yokota T, Iuchi K, Nishimaki K, Takami S, Akashiba H, Shitaka Y, Katsura K, Kimura K, Ohta S.
  • Journal Title: Neurosci Lett. Volume: 587 Pages: 126-131
  • Peer Reviewed / Open Access
• [Journal Article] Protective effect of molecular hydrogen against oxidative stress caused by peroxynitrite derived from nitric oxide in rat retina. (2015)
  • Author(s): Yokota, T., Kamimura, N., Igarashi, T., Takahashi, H., Ohta, S., Oharazawa, H.
  • Journal Title: Clin Experiment Ophthalmol. Volume: 20 Pages: 12525-12530
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Inhalation During Normoxic Resuscitation Improves Neurological Outcome in a Rat Model of Cardiac Arrest, Independent of Targeted Temperature Management. (2014)
  • Author(s): M., Kamimura, N., Yokota, T., Suzuki, M., Ohta, S., Fukuda, K., Hori, S.
  • Journal Title: Circulation Volume: 130 Pages: 2173-2180
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] H2 gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia (2012)
  • Author(s): Hayashida K, Sano M, Kamimura N, Yokota T, Suzuki M, Maekawa Y, Kawamura A, Abe T, Ohta S, Fukuda K, Hori S
  • Journal Title: J. Am. Heart Assoc Volume: 1(5) Issue: 5
  • DOI: 10.1161/jaha.112.003459
  • Peer Reviewed
• [Presentation] Molecular hydrogen protects retina from oxidative stress and mitochondrial damage through reducing peroxynitrite derived from nitric oxide. (2014)
  • Author(s): Takashi Yokota, Hideaki Oharazawa, Naomi Kamimura, Tsutomu Igarashi, Hiroshi Takahashi, Shigeo Ohta
  • Organizer: Euromit 2014
  • Place of Presentation: フィンランド タンペレ市
  • Year and Date: 2014-06-15 – 2014-06-20
• [Presentation] Trancegenic mice expressing the redox-sensitive green fluorescent protein in the cytosol and mitochondria (2014)
  • Author(s): Kiyomi Nishimaki, Alexander M Wolf , Takashi Yokota, Naomi Kamimura and Shigeo Ohta
  • Organizer: Euromit 2014
  • Place of Presentation: フィンランド タンペレ市
  • Year and Date: 2014-06-15 – 2014-06-20
• [Presentation] アルツハイマー病モデルに対する骨髄単核球移植の予防・治療効果 (2013)
  • Author(s): 上村尚美、西巻貴代美、金丸拓也、横田隆、井内勝哉、高見新也、赤芝洋紀、志鷹義嗣、桂研一郎、片山泰朗、太田成男
  • Organizer: 第36回日本分子生物学会
  • Place of Presentation: 神戸国際会議場
• [Presentation] Effects of Intravenous Traansplantation of Bone Marrow Mononuclear cell on Alzheimer's disease mouse models (2013)
  • Author(s): Kanamaru Takuya,Kamimura Naomi, Iuchi Katsuya,Nishimaki Kiyomi, Yokota Takashi, Takami Shinya, Akashiba Hiroki, Shitaka Yoshitugu, Katsura Ken-ichiro,Katayama Yasuo, Ohta Shigeo
  • Organizer: The 11th International Conference on Alzheimer's and Parkinson's Disease
  • Place of Presentation: Italia（Firenze）
• [Presentation] Accelerated Alzheimer-type Phenotype in transgenic mice carrying both mutant amyloid precursor protein and dominant-negative form of mitochondrial aldehydrogenase 2 (2013)
  • Author(s): Kamimura Naomi,Nishimaki Kiyom, Kanamaru Takuya,Iuchi Katsuya, Yokota Takashi, Takami Shinya, Akashiba Hiroki, Shitaka Yoshitugu, Katsura Ken-ichiro,Katayama Yasuo, Ohta Shigeo
  • Organizer: International Symposium on Mitochondria 2013
  • Place of Presentation: Tokyo (rotsupongi Hilzu)
• [Presentation] ラット心拍停止モデルを用いた水素吸入療法と低体温療法の予後改善効果の検討 (2013)
  • Author(s): 林田敬、佐野元昭、上村尚美、横田隆、太田成男、福田恵一、堀進吾
  • Organizer: 第3回分子状水素医学シンポジウム
  • Place of Presentation: 東京（品川区きゅりあん）
• [Presentation] APP TRANSGENIC MICE WITH OXIDATIVE STRESS (2013)
  • Author(s): Naomi Kamimura, Takuya Kanamaru, Takashi Yokota, Katsuya Iuchi, Kiyomi Nishimaki, Shinya Takami, Hiroki Akashiba, Yoshitsugu Shitaka, Ken-ichiro Katsura, Yasuo Katayama, and Shigeo Ohta.
  • Organizer: AD/PD2013 (The 11th International Conference On Alzheimer’s & Parkinson’s Disease
  • Place of Presentation: Florence, Italy
• [Presentation] EFFECTS OF INTRAVENOUS TRANSPLANTATION OF BONE MARROW MONONUCLEAR CELL ON ALZHEIMER’S DISEASE MOUSE MODELS. (2013)
  • Author(s): Takuya Kanamaru, Naomi Kamimura, Katsuya Iuchi, Kiyomi Nishimaki, Takashi Yokota, Shinya Takami, Hiroki Akashiba, Yoshitsugu Shitaka, Ken-ichiro Katsura, Yasuo Katayama, and Shigeo Ohta
  • Organizer: AD/PD2013 (The 11th International Conference On Alzheimer’s & Parkinson’s Disease
  • Place of Presentation: Florence, Italy
• [Presentation] ラット心停止モデルを用いた水素吸入療法と低体温療法の予後改善効果の検討 (2013)
  • Author(s): 林田敬、佐野元昭、上村尚美、横田隆、太田成男、福田恵一、堀進悟
  • Organizer: 第３回分子状水素医学シンポジウム
  • Place of Presentation: 東京
• [Presentation] ミトコンドリアアルデヒド脱水素酵素２活性欠損マウス（DAL101マウス）に対する骨髄単核球移植の認知機能改善効果 (2012)
  • Author(s): 金丸拓也、上村尚美、井内勝哉、西槙貴代美、横田隆、高見新也、赤芝洋紀、志鷹義嗣、桂研一郎、片山泰朗、太田成男
  • Organizer: 第12回日本ミトコンドリア学会年会
  • Place of Presentation: つくば
• [Presentation] ヒト変異APP高発現マウスと酸化ストレス亢進マウスとの掛け合わせマウスの解析 (2012)
  • Author(s): 上村尚美、金丸拓也、横田隆、井内勝哉、西槙貴代美、高見新也、赤芝洋紀、志鷹義嗣、桂研一郎、片山泰朗、太田成男
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] アルツハイマーモデルマウスに対する他家骨髄単核球投与の認知機能改善効果 (2012)
  • Author(s): 金丸拓也、上村尚美、井内勝哉、西槙貴代美、横田隆、高見新也、赤芝洋紀、志鷹義嗣、桂研一郎、片山泰朗、太田成男
  • Organizer: 第35回日本分子生物学会
  • Place of Presentation: 福岡
• [Presentation] 心停止蘇生後症候群に対する水素吸入療法の有効性の検討 (2012)
  • Author(s): 林田敬、佐野元昭、上村尚美、横田隆、太田成男、福田恵一、堀進悟
  • Organizer: 第40回日本救急医学会総会
  • Place of Presentation: 京都
• [Presentation] ラット心停止モデルを用いた水素吸入療法と低体温療法の予後改善効果の検討 (2012)
  • Author(s): 林田敬、佐野元昭、上村尚美、横田隆、太田成男、福田恵一、堀進悟
  • Organizer: 第27回日本Shock学会
  • Place of Presentation: 東京
• [Remarks] 日本医科大学老人病研究所 細胞生物学ホームページ
  • URL: http://home.nms.ac.jp/ig/siboseibutsu/kenkyu.html
• [Remarks] 日本医科大学大学院医学研究科 加齢科学系専攻細胞生物学分野
  • URL: http://home.nms.ac.jp/ig/saiboseibutsu/index.html