Development and prevention of disease states caused by endoplasmic reticulum stress

• Project/Area Number: 21659043
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: General anatomy (including Histology/Embryology)
• Research Institution: University of Tsukuba
• Principal Investigator: KOBAYASHI Makoto 筑波大学, 医学医療系, 講師 (50254941)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥300,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,000,000 (Direct Cost: ¥1,000,000); Fiscal Year 2009: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: 小胞体ストレス / 酸化ストレス / Nrf2 / ゼブラフィッシュ / 突然変異系統 / 病態モデル / 遺伝学 / ストレスモニター

Research Abstract

Residual bodies of lysosomes were found to be accumulated in the liver cells in the zebrafish mutant it768 in which endoplasmic reticulum (ER) stress were spontaneously upregulated. The results were interesting since accumulation of residual bodies had been implied to be associated with oxidative stress. To elucidate relationship between ER stress and oxidative stress, we generated and analyzed a mutant zebrafish of Nrf2, a master regulator of antioxidant genes, and the double mutant of Nrf2 and it768.

Research Products

• [Journal Article] Tissue-restricted expression of Nrf2 and its target genes in zebrafish with gene-specific variations in the induction profiles (2011)
  • Author(s): Nakajima H, Nakajima-Takagi Y, Tsujita T, Akiyama S, Wakasa T, Mukaigasa K, Kaneko H, Tamaru Y, Yamamoto M, Kobayashi M
  • Journal Title: PLoS One Volume: 6 Issue: 10 Pages: e26884-e26884
  • DOI: 10.1371/journal.pone.0026884
  • Peer Reviewed
• [Journal Article] Molecular basis for Flk1 expression in hemato-cardiovascular progenitors in the mouse (2011)
  • Author(s): Ishitobi H, Wakamatsu A, Lui F, Azami T, Hamada M, Matsumoto K, Kataoka H, kobayashi M, Choi K, Nishikawa S-I, Takahashi S, Ema M
  • Journal Title: Development Volume: 138 Issue: 24 Pages: 5357-5368
  • DOI: 10.1242/dev.065565
  • Peer Reviewed
• [Journal Article] Nitro-fatty acids and cyclopentenone prostaglandins share strategies to activate the Keap1-Nrf2 system : a study using green fluorescent protein transgenic zebrafish (2011)
  • Author(s): Tsujita T, Li L, Nakajima H, Iwamoto N, Nakajima-Takagi Y, Ohashi K, Kawakami K, Kumagai Y, Freeman BA, Yamamoto M, Kobayashi M
  • Journal Title: Genes Cells Volume: 16 Issue: 1 Pages: 46-57
  • DOI: 10.1111/j.1365-2443.2010.01466.x
  • NAID: 120007130821
  • Peer Reviewed
• [Journal Article] Tissue-restricted induction of Nrf2 and its target genes in zebrafish with gene-specific variations in the induction profiles (2011)
  • Author(s): Nakajima H, Nakajima-Takagi Y, Tsujita T, Akiyama S, Wakasa T, Mukaigasa M, Kaneko H, Tamaru Y, Yamamoto M, Kobayashi M
  • Journal Title: PLoS ONE Volume: 6
  • Peer Reviewed
• [Journal Article] Nitro-fatty acids and cyclopentenone prostaglandins share strategies to activate the Keap 1-Nrf2 system : a study using green fluorescent protein transgenic zebrafish (2011)
  • Author(s): Tsujita, T
  • Journal Title: Genes Cells Volume: 16 Pages: 46-57
  • Peer Reviewed
• [Journal Article] Efficient transient rescue of hematopoietic mutant phenotypes in zebrafish using Tol2-mediated transgenesis (2010)
  • Author(s): Takeuchi, M., Kaneko, H., Nishikawa, K., Kawakami, K., Yamamoto, M. andKobayashi, M.
  • Journal Title: Dev.Growth Differ Volume: 52 Issue: 2 Pages: 245-250
  • DOI: 10.1111/j.1440-169x.2009.01168.x
  • NAID: 10027563994
  • Peer Reviewed
• [Journal Article] Harnessing the antioxidant power with ARE-inducingcompounds (2010)
  • Author(s): Kobayashi, M
  • Journal Title: Chem. Biol Volume: 17 Issue: 5 Pages: 419-420
  • DOI: 10.1016/j.chembiol.2010.05.003
• [Journal Article] Metalloprotease-dependent onset of blood circulation in zebrafish (2010)
  • Author(s): Iida, A.
  • Journal Title: Curr. Biol. Volume: 52 Pages: 245-250
  • Peer Reviewed
• [Journal Article] Harnessing the antioxidant power with ARE-inducing compounds (2010)
  • Author(s): Kobayashi, M.
  • Journal Title: Chem. Biol. Volume: 17 Pages: 419-420
• [Journal Article] Nrf2システムはどうやって多種多様の化学物質に応答するのか? (2010)
  • Author(s): 中島やえ子
  • Journal Title: 医学のあゆみ Volume: 233 Pages: 639-640
• [Journal Article] Efficient transient rescue of hematopoietic mutant phenotypes in zebrafish using To12-mediated transgenesis (2010)
  • Author(s): Takeuchi, M.
  • Journal Title: Dev.Growth Differ. 52 Pages: 245-250
  • Peer Reviewed
• [Journal Article] The keratin-relatedOuroboros proteins function as immune antigens mediating tail regression in Xenopus metamorphosis (2009)
  • Author(s): Mukaigasa, K., Hanasaki, A., Maeno, M., Fujii, H., Hayashida, S., Itoh, M., Kobayashi, M., Tochinai, S., Hatta, M., Iwabuchi, K., Taira, M., Onoe, K. and Izutsu, Y.
  • Journal Title: Proc. Natl. Acad.Sci Volume: 106 Issue: 43 Pages: 18309-18414
  • DOI: 10.1073/pnas.0708837106
  • Peer Reviewed
• [Journal Article] The keratin-related Ouroboros proteins function as immune antigens mediating tail regression in Xenopus metamorphosis (2009)
  • Author(s): Mukaigasa, K.
  • Journal Title: Proc.Natl.Acad.Sci.USA 106 Pages: 18309-18414
  • Peer Reviewed
• [Presentation] Nrf2標的遺伝子の組織特異的発現誘導 (2011)
  • Author(s): 中島瞳, 向笠勝貴, 小林麻己人
  • Organizer: 転写研究会若手シンポジウム
  • Place of Presentation: 東京
  • Year and Date: 2011-02-18
• [Presentation] 酸化ストレスに対して高い感受性を示すNrf2変異ゼブラフィッシュ (2011)
  • Author(s): 向笠勝貴, Nguyen Linh Thi Phuong, 李麗, 中島瞳, 小林麻己人
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Nrf2によるゼブラフィッシュヘムオキシゲナーゼ1の肝臓特異的な発現誘導 (2011)
  • Author(s): 中島瞳, 中島やえ子, 小林麻己人
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Gene regulation of Gata1 by a histonedemethylase LSD1 in zebrafish (2010)
  • Author(s): Takeuchi, M., Watanabe, M., Ohashi, K., Yamamoto, M.and Kobayashi, M.
  • Organizer: The 5th International Symposium on GATA Factors : Function and Regulation of GATA factors in Development and Diseases
  • Place of Presentation: Sendai
• [Presentation] 誘導プロファイルの違いにより分類されるNrf2標的遺伝子群 (2010)
  • Author(s): 中島瞳, 李麗, 向笠勝貴, 小林麻己人
  • Organizer: 第16回小型魚類研究会
  • Place of Presentation: 埼玉
• [Presentation] 赤血球分化を進行させる転写因子Gata1の分化に伴う発現制御の変遷 (2010)
  • Author(s): 大橋健, 竹内未紀, 渡辺真奈, 小林麻己人
  • Organizer: 第16回小型魚類研究会
  • Place of Presentation: 埼玉
• [Presentation] A spontaneous ER stress caused by a genetic mutation in zebrafish induces a constitutive activation of the Nrf2 defense system (2010)
  • Author(s): Li, L., Mukaigasa, K., Tsujita, T., Nakajima, H., Yamamoto, M. and Kobayashi, M
  • Organizer: The 3rd InternationalSymposium on Protein Communication
  • Place of Presentation: Nara
• [Presentation] Nrf2 transcription activation system comprises a multiple sensing mechanism (2010)
  • Author(s): Li, L., Nakajima, H. and Kobayashi, M
  • Organizer: The 11th Asian and Oceanian Conference on Transcription
  • Place of Presentation: Okinawa
• [Presentation] Li, L., Nakajima, H., Freeman, B.A. andKobayashi, M (2010)
  • Author(s): Li, L., Nakajima, H., Freeman, B.A. andKobayashi, M
  • Organizer: 9th International Conference on Zebrafish Development & Genetics
  • Place of Presentation: Madison
• [Presentation] Takeuchi1, M., Kaneko, H., Nishikawa, K., Kawakami, K., Yamamoto, M. andKobayashi, M (2010)
  • Author(s): Takeuchi1, M., Kaneko, H., Nishikawa, K., Kawakami, K., Yamamoto, M. andKobayashi, M
  • Organizer: 第43回日本発生生物学会年会
  • Place of Presentation: 京都
• [Presentation] Nitro-fatty acids-induced Nrf2 activation in GFP transgenic zebrafish (2010)
  • Author(s): Li, L.
  • Organizer: 9th International Conference on Zebrafish Development & Genetics
  • Place of Presentation: 米国Madison
• [Presentation] A spontaneous ER stress caused by a genetic mutation in zebrafish induces a constitutive activation of the Nrf2 defense system (2010)
  • Author(s): Li, L.
  • Organizer: The 3rd International Symposium on Protein Communication
  • Place of Presentation: Nara
• [Presentation] Keap1-Nrf2システムの多様な感知応答機構 (2009)
  • Author(s): 李麗, 中島瞳, 中島やえこ, 岩本典子, 熊谷嘉人, 山本雅之, 小林麻己人
  • Organizer: 平成21年度日本生化学会関東支部例会「若手が担う次世代型生化学研究」
  • Place of Presentation: つくば
  • Year and Date: 2009-06-20
• [Presentation] 赤血球系列への分化が滞る突然変異ゼブラフィッシュ (2009)
  • Author(s): 竹内未紀, 山本雅之, 小林麻己人
  • Organizer: 平成21年度日本生化学会関東支部例会「若手が担う次世代型生化学研究」
  • Place of Presentation: つくば
  • Year and Date: 2009-06-20
• [Presentation] ヒト先天性グリコシル化異常症の病態モデルゼブラフィッシュの解析 (2009)
  • Author(s): 向笠勝貴, 辻田忠志, 李麗, 山本雅之, 小林麻己人
  • Organizer: 平成21年度日本生化学会関東支部例会「若手が担う次世代型生化学研究」
  • Place of Presentation: つくば
  • Year and Date: 2009-06-20
• [Presentation] ヒト先天性グリコシル化異常症の病態モデルゼブラフィッシュの解析 (2009)
  • Author(s): 向笠勝貴
  • Organizer: 平成21年度日本生化学会関東支部例会
  • Place of Presentation: つくば
  • Year and Date: 2009-06-20
• [Presentation] An easy and effective approach to rescue zebrafish mutant phenotypes via transient transgenesis using Tol2 constructs (2009)
  • Author(s): Takeuchi, M., Kaneko, H., Nishikawa, K., Kawakami, K., Yamamoto, M. andKobayashi, M
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] Identification of Nrf2-regulated genes in zebrafish (2009)
  • Author(s): Nakajima, H., Nakajima-Takagi, Y., Akiyama, S., Wakasa, T., Li, L., Tsujita, T., Kaneko, H., Tamaru, Y., Yamamoto, M.and Kobayashi, M
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] A zebrafish model for human congenital disorder ofglycosylation (2009)
  • Author(s): Mukaigasa, K., Li, L., Yagi, H., Tsujita, T., Kato, K., Yamamoto, M. andKobayashi, M
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] GF Ptransgenic zebrafish is a good tool toclassify Nrf2 activators (2009)
  • Author(s): Li, L., Nakajima, H., Tusjita, T., Yamamoto, M. and Kobayashi, M
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Presentation] 親電子性物質による非触媒性Cys121の翻訳後修飾を介したPTP1B/EGFRシグナルの活性化 (2009)
  • Author(s): 岩本典子, 伊藤創平, 小林麻己人, 熊谷嘉人
  • Organizer: 第82回日本生化学会大会
  • Place of Presentation: 神戸
• [Presentation] ヒト先天性糖鎖形成不全症CDG-Iaの病態モデルフィッシュ (2009)
  • Author(s): 李麗, 辻田忠志, 向笠勝貴, 矢木宏和, 加藤晃一, 山本雅之, 小林麻己人
  • Organizer: 第15回小型魚類研究会
  • Place of Presentation: 名古屋
• [Presentation] Tol2システムを利用した一過性レスキュー解析 (2009)
  • Author(s): 竹内未紀, 金子寛, 西川恵三, 川上浩一, 山本雅之, 小林麻己人
  • Organizer: 第15回小型魚類研究会
  • Place of Presentation: 名古屋
• [Presentation] ゼブラフィッシュを用いたヒト先天性糖鎖形成不全症CDG-Iaの治療戦略の探索 (2009)
  • Author(s): 向笠勝貴, 辻田忠志, 李麗, 山本雅之, 小林麻己人
  • Organizer: 第15回小型魚類研究会
  • Place of Presentation: 名古屋
• [Presentation] ストレス応答型転写因子Nrf2の標的遺伝子群の多様性 (2009)
  • Author(s): 中島瞳, 中島-高木やえ子, 井手玲子, 辻田忠志, 金子寛, 秋山真一, 若狭武司、田丸浩、山本雅之、小林麻己人
  • Organizer: 第15回小型魚類研究会
  • Place of Presentation: 名古屋
• [Presentation] Genetically induced ER stress in azebrafish model for human congenital disorders of glycosylation (2009)
  • Author(s): Mukaigasa, K., Li, L., Tsujita, T., Yamamoto, M. and Kobayashi, M
  • Organizer: 日本発生生物学会第42回大会
  • Place of Presentation: 新潟
• [Presentation] Mutation of thelysine-specific demethylase 1 genecauses lineage-specific defects in zebrafish hematopoiesis (2009)
  • Author(s): Takeuchi, M., Kaneko, H., Kobayashi, M. and Yamamoto, M
  • Organizer: 日本発生生物学会第42回大会
  • Place of Presentation: 新潟
• [Presentation] Genetically induced ER stress in a zebrafish model for human congenital disorders of glycosylation (2009)
  • Author(s): Mukaigasa, K.
  • Organizer: 日本発生生物学会第42回大会
  • Place of Presentation: 新潟
• [Presentation] A zebrafish model for human congenital disorder of glycosylation. (2009)
  • Author(s): Mukaigasa, K.
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/MDBiology/mdbiol.index.html
• [Remarks]
  • URL: http://www.md.tsukuba.ac.jp/MDBiology/mdbiol.index.html