The mechanism of generation of reactive oxygen species and oxidative neuronal injury induced by methylmercury

• Project/Area Number: 26740024
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Hiroshima University
• Principal Investigator: Ishihara Yasuhiro 広島大学, 総合科学研究科, 助教 (80435073)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: メチル水銀 / 活性酸素 / 酸化ストレス / ミトコンドリア / MRI / 神経毒性

Outline of Final Research Achievements

The purpose of this study is to reveal the mechanism of oxidative neuronal injury induced by methylmercury. Reactive oxygen species (ROS) derived from mitochondria were shown to be involved in neurotoxicity induced by methylmercury using mitochondrial DNA depleted SH-SY5Y cells. Brain region specific oxidation was detected in mice administered with methylmercury. The relationships between region specific generation of ROS and behavior disorder induced by methylmercury will be examined in the future.

Research Products

• [Journal Article] Transcription factor activation in rat primary astrocytes exposed to methylmercury. (2016)
  • Author(s): Takemoto T, Ishihara Y, Tsuji M, Kawamoto T, Yamazaki T.
  • Journal Title: Fundam. Toxicol. Sci. Volume: 3 Pages: 63-65
  • NAID: 130005133715
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Dual role of SOD2 induced in activated microglia: increased tolerance to oxidative stress and convergence of inflammatory responses. (2015)
  • Author(s): Ishihara Y, Takemoto T, Itoh K, Ishida A, Yamazaki T.
  • Journal Title: J. Biol. Chem. Volume: 290 Issue: 37 Pages: 22805-22817
  • DOI: 10.1074/jbc.m115.659151
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Neuroprotection elicited by nerve growth factor and brain-derived neurotrophic factor released from astrocytes in response to methylmercury. (2015)
  • Author(s): Takemoto T, Ishihara Y, Ishida A, Yamazaki T.
  • Journal Title: Environ. Toxicol. Pharmacol. Volume: 40 Issue: 1 Pages: 199-205
  • DOI: 10.1016/j.etap.2015.06.010
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Protective actions of 17β-estradiol and progesterone on oxidative neuronal injury induced by organometallic compounds (Review Article). (2015)
  • Author(s): Ishihara Y, Takemoto T, Ishida A, Yamazaki T.
  • Journal Title: Oxid. Med. Cell. Longev. Volume: 343706 Pages: 1-16
  • DOI: 10.1155/2015/343706
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Selective estrogen-receptor modulators suppress microglial activation and neuronal cell death via an estrogen receptor-dependent pathway. (2015)
  • Author(s): Ishihara Y, Itoh K, Ishida A, Yamazaki T.
  • Journal Title: J Steroid Biochem Mol Biol. Volume: 145 Pages: 85-93
  • Peer Reviewed
• [Journal Article] Prevention of status epilepticus-induced brain edema and neuronal cell loss by repeated treatment with high-dose levetiracetam. (2015)
  • Author(s): Itoh K, Inamine M, Oshima W, Kotani M, Chiba Y, Ueno M, Ishihara Y.
  • Journal Title: Brain Res. Volume: 1608 Pages: 225-234
  • Peer Reviewed
• [Journal Article] Suppressive effects of 17β-estradiol on tributyltin-induced neuronal injury via Akt activation and attenuation of oxidative stress in rat hippocampal slices. (2014)
  • Author(s): Ishihara Y, Fujitani N, Kawami T, Adachi C, Ishida A, Yamazaki T.
  • Journal Title: Life Sci. Volume: 99 Pages: 24-30
  • Peer Reviewed
• [Journal Article] Glycolytic genes are targets of the nuclear receptor Ad4BP/SF-1. (2014)
  • Author(s): Baba T, Otake H, Sato T, Miyabayashi K, Shishido Y, Wang CY, Shima Y, Kimura H, Yagi M, Ishihara Y, Hino S, Ogawa H, Nakao M, Yamazaki T, Kang D, Ohkawa Y, Suyama M, Chung BC, Morohashi K.
  • Journal Title: Nat. Commun. Volume: 5 Pages: 3634-3634
  • NAID: 130005085557
  • Peer Reviewed
• [Presentation] メチル水銀によるアストロサイト適応応答とその神経保護作用. (2016)
  • Author(s): 石原 康宏、竹本 拓矢、山﨑 岳.
  • Organizer: 平成26年度 環境省「重金属等による健康影響に関する総合的研究」メチル水銀研究ミーティング.
  • Place of Presentation: 東京
  • Year and Date: 2016-01-07
• [Presentation] メチル水銀による酸化ストレス誘導メカニズムの解明とそのin vivo神経影響評価. (2015)
  • Author(s): 石原 康宏
  • Organizer: 第34回 生体と金属・化学物質に関する研究会
  • Place of Presentation: 滋賀
  • Year and Date: 2015-08-21
• [Presentation] メチル水銀により生じる聴覚伝導路異常の解析. (2015)
  • Author(s): 石原 康宏、伊藤 康一、高橋 亮平、石田 敦彦、山崎 岳.
  • Organizer: 第42回 日本毒性学会学術年会
  • Place of Presentation: 金沢
  • Year and Date: 2015-06-29
• [Presentation] 有機スズによる酸化的神経障害とその内因性防御因子としてのニューロステロイド. (2015)
  • Author(s): 石原 康宏.
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸学院大学
  • Year and Date: 2015-03-25 – 2015-03-28
  • Invited
• [Presentation] メチル水銀の聴覚伝導路への影響. (2014)
  • Author(s): 石原 康宏、伊藤 康一、高橋 亮平、山崎 岳.
  • Organizer: 平成26年度メチル水銀研究ミーティング
  • Place of Presentation: LMJ東京研修センター
  • Year and Date: 2014-12-05
• [Presentation] 核磁気共鳴画像法を用いたメチル水銀投与により生じる脳内酸化と神経機能異常測定の試み. (2014)
  • Author(s): 石原 康宏、伊藤 康一、高橋 亮平、石田 敦彦、山﨑 岳.
  • Organizer: フォーラム2014：衛生薬学・環境トキシコロジー
  • Place of Presentation: つくば国際会議場
  • Year and Date: 2014-09-19 – 2014-09-20
• [Remarks] 広島大学 大学院総合科学研究科 分子脳科学研究室 HP
  • URL: http://home.hiroshima-u.ac.jp/ishiyasu/
• [Remarks] 広島大学 大学院総合科学研究科 分子脳科学研究室 HP
  • URL: http://home.hiroshima-u.ac.jp/ishiyasu/