Elucidation of pathological mechanisms by integration glycans and redox

• Project/Area Number: 15K14481
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional biochemistry
• Research Institution: Osaka International Cancer Institute (2018); Institute of Physical and Chemical Research (2015-2017)
• Principal Investigator: Taniguchi Naoyuki 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 糖鎖オンコロジー部部長 (90002188)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 糖鎖 / 糖転移酵素 / レドックス / SOD3

Outline of Final Research Achievements

We have revealed that the antioxidative functions of SOD3 were modulated by N-glycans carried on them. SOD3 lacking complex type glycans expressed different anticancer effects compared with SOD3 carrying complex type glycans, which indicated N-glycans on SOD3 were involved in development of cancers. We also revealed that oxidative stress changed the expression levels of multiple glycosyltransferases in macrophage, which enhanced phagocytosis. These results demonstrate the biological linkage between glycans and redox. We are now trying to publish these results.

Academic Significance and Societal Importance of the Research Achievements

本研究は、「糖鎖」と「レドックス」という細胞が持つ一見独立した2つのシステムが密接に制御し合う協調システムを新たに見出し、Glyco-Redox制御異常を背景とする様々な疾患の病因解明と治療法探索に繋がる新しい知見を得ることを目的としていた。本研究で明らかになった、抗酸化酵素SOD3の糖鎖による機能制御、および酸化ストレスによるマクロファージの糖鎖解析と機能解明は、まさに目的としたGlyco-Redoxシステムの一端を明らかにしたものであり、今後、関連疾患の病因解明に繋がることが期待される。

Research Products

• [Journal Article] Generation of the heterogeneity of extracellular vesicles by membrane organization and sorting machineries (2019)
  • Author(s): Harada Yoichiro、Suzuki Takehiro、Fukushige Tomoko、Kizuka Yasuhiko、Yagi Hirokazu、Yamamoto Mika、Kondo Kiyotaka、Inoue Hiromasa、Kato Koichi、Taniguchi Naoyuki、Kanekura Takuro、Dohmae Naoshi、Maruyama Ikuro
  • Journal Title: Biochimica et Biophysica Acta (BBA) - General Subjects Volume: 1863 Issue: 4 Pages: 681-691
  • DOI: 10.1016/j.bbagen.2019.01.015
  • Peer Reviewed
• [Journal Article] Implication of C-type lectin receptor langerin and keratan sulfate disaccharide in emphysema (2018)
  • Author(s): Kizuka Yasuhiko、Mishra Sushil、Yamaguchi Yoshiki、Taniguchi Naoyuki
  • Journal Title: Cellular Immunology Volume: 333 Pages: 80-84
  • DOI: 10.1016/j.cellimm.2018.07.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Neural functions of bisecting GlcNAc. (2018)
  • Author(s): Kizuka Y, Taniguchi N
  • Journal Title: Glycoconj. J. Volume: ー Issue: 4 Pages: 345-351
  • DOI: 10.1007/s10719-018-9829-4
  • Peer Reviewed
• [Journal Article] High affinity sugar ligands of C-type lectin receptor langerin. (2018)
  • Author(s): Ota F, Hirayama T, Kizuka Y, Yamaguchi Y, Fujinawa R, Nagata M; Ismanto HS, Lepenies, Aretz J, Rademacher C, Seeberger PH; Angata T, Kitazume S, Yoshida K, Betsuyaku T, Kida K Yamasaki S, and Taniguchi N
  • Journal Title: BBA - General Subjects Volume: - Issue: 7 Pages: 1592-1601
  • DOI: 10.1016/j.bbagen.2018.04.004
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 1.Imamaki R. Ogawa K, Kizuka Y, Komi Y, Kojima S, Kotani N, Honke K, Honda T, Taniguchi N, and Kitazume S (2018)
  • Author(s): 1.Imamaki R. Ogawa K, Kizuka Y, Komi Y, Kojima S, Kotani N, Honke K, Honda T, Taniguchi N, and Kitazume S
  • Journal Title: Oncogene Volume: - Issue: 31 Pages: 4287-4299
  • DOI: 10.1038/s41388-018-0271-7
  • Peer Reviewed / Open Access
• [Journal Article] Metabolic control of T cell immune response through glycans in inflammatory bowel disease. (2018)
  • Author(s): Dias AM, Correia A, Pereira MS, Almeida CR, Alves I, Pinto V, Catarino TA, Mendes S, Leander M, Oliva-Teles MT, Maia L, Delerue-Matos C, Taniguchi N, Lima M, Pedroto I, Marcos-Pinto R, Lago P, Reis CA, Vilanova M, Pinho SS
  • Journal Title: Proc Natl Acad Sci U S A Volume: 115(20) Issue: 20
  • DOI: 10.1073/pnas.1720409115
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Structure and mechanism of cancer-associated N-acetylglucosaminyltransferase-V (2018)
  • Author(s): Nagae Masamichi、Kizuka Yasuhiko、Mihara Emiko、Kitago Yu、Hanashima Shinya、Ito Yukishige、Takagi Junichi、Taniguchi Naoyuki、Yamaguchi Yoshiki
  • Journal Title: Nature Communications Volume: 9 Issue: 1 Pages: 3380-3380
  • DOI: 10.1038/s41467-018-05931-w
  • Peer Reviewed / Open Access
• [Journal Article] Core fucose is essential glycosylation for CD14-dependent Toll-like receptor 4 and Toll-like receptor 2 signaling in macrophages (2018)
  • Author(s): Nakayama K, Wakamatsu K, Fujii H, Shinzaki S, Takamatsu S, Kitazume S, Kamada Y, Takehara T, Taniguchi N, Miyoshi E
  • Journal Title: J Biochem Volume: ー Issue: 3 Pages: 227-237
  • DOI: 10.1093/jb/mvy098
  • NAID: 40021845862
  • Peer Reviewed
• [Journal Article] Core fucosylation of the T cell receptor is required for T cell activation. (2018)
  • Author(s): 8.Liang W., Mao S., Sun S., Li M., Li Z., Yu R., Ma T., Gu J., Zhang J., Taniguchi N., Li W.
  • Journal Title: Front Immunol., Volume: 9 Pages: 78-78
  • DOI: 10.3389/fimmu.2018.00078
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Identification and characterization of UDP-mannose in human cell lines and mouse organs: Differential distribution across brain regions and organs (2018)
  • Author(s): Nakajima Kazuki、Kizuka Yasuhiko、Yamaguchi Yoshiki、Hirabayashi Yoshio、Takahashi Kazuo、Yuzawa Yukio、Taniguchi Naoyuki
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 495 Issue: 1 Pages: 401-407
  • DOI: 10.1016/j.bbrc.2017.10.173
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Sialylation of extracellular superoxide dismutase (EC-SOD) enhances furin-mediated cleavage and secretion (2017)
  • Author(s): Ota Fumi、Kizuka Yasuhiko、Nakano Miyako、Yamaguchi Yoshiki、Kitazume Shinobu、Ookawara Tomomi、Taniguchi Naoyuki
  • Journal Title: Glycobiology Volume: 27 Issue: 12 Pages: 1081-1088
  • DOI: 10.1093/glycob/cwx087
  • Peer Reviewed / Open Access
• [Journal Article] Core fucose is critical for CD14-dependent Toll-like receptor 4 signaling (2017)
  • Author(s): 4.Iijima J, Kobayashi S, Kitazume S*, Kizuka Y, Fujinawa R, Korekane H, Shibata T, Saitoh S, Akashi-Takamura S, Miyake K, Miyoshi E, and Taniguch N
  • Journal Title: Glycobiology Volume: 2017 Issue: 11 Pages: 1006-1015
  • DOI: 10.1093/glycob/cwx075
  • Peer Reviewed / Open Access
• [Journal Article] N -glycan and Alzheimer's disease (2017)
  • Author(s): Kizuka Yasuhiko、Kitazume Shinobu、Taniguchi Naoyuki
  • Journal Title: Biochimica et Biophysica Acta (BBA) - General Subjects Volume: 1861 Issue: 10 Pages: 2447-2454
  • DOI: 10.1016/j.bbagen.2017.04.012
  • Peer Reviewed
• [Journal Article] The Inhibitory Role of α2,6-Sialylation in Adipogenesis. (2017)
  • Author(s): Kaburagi T, Kizuka Y, Kitazume S, Taniguchi N.
  • Journal Title: Journal of Biological Chemistry Volume: 292 Issue: 6 Pages: 2278-2286
  • DOI: 10.1074/jbc.m116.747667
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] N-Glycosylation is essential for the secretion of extracellular superoxide dismutase. (2016)
  • Author(s): Ota F, Kizuka Y, Kitazume S, Adachi T, Taniguchi N.
  • Journal Title: FEBS Letters Volume: 590 Issue: 19 Pages: 3357-3367
  • DOI: 10.1002/1873-3468.12378
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Glycation vs. glycosylation: a tale of two different chemistries and biology in Alzheimer's disease. (2016)
  • Author(s): Taniguchi N, Takahashi M, Kizuka Y, Kitazume S, Shuvaev VV, Ookawara T, Furuta A.
  • Journal Title: Glycoconjugate Journal Volume: 33 Issue: 4 Pages: 487-497
  • DOI: 10.1007/s10719-016-9690-2
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Glyco-redox, a link between oxidative stress and changes of glycans: Lessons from research on glutathione, reactive oxygen and nitrogen species to glycobiology. (2016)
  • Author(s): N. Taniguchi, Y. Kizuka, S. Takamatsu, E. Miyoshi, C. Gao, K. Suzuki, S. Kitazume, K. Ohtsubo
  • Journal Title: Arch. Biochem. Biphys. Volume: 595 Pages: 72-80
  • DOI: 10.1016/j.abb.2015.11.024
  • Peer Reviewed / Open Access
• [Journal Article] Bisecting GlcNAc modification stabilizes BACE1 protein under oxidative stress conditions (2016)
  • Author(s): Kizuka Y, Nakano M, Kitazume S, Saito T, Saido TC, Taniguchi N
  • Journal Title: Biochemical Journal Volume: 473 Issue: 1 Pages: 21-30
  • DOI: 10.1042/bj20150607
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] In vivo imaging of advanced glycation end products (AGEs) of albumin: first observations of significantly reduced clearance and liver deposition properties in mice (2016)
  • Author(s): Tsutsui A, Ogura A, Tahara T, Nozaki S, Urano S, Hara M, Kojima S, Kurbangalieva A, Onoe H, Watanabe Y, Taniguchi N, Tanaka K
  • Journal Title: Organic and Biomolecular Chemistry Volume: - Issue: 24 Pages: 5755-5760
  • DOI: 10.1039/c6ob00098c
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of Fucosyltransferase 8 Is Associated with an Unfavorable Clinical Outcome in Non-Small Cell Lung Cancers (2015)
  • Author(s): Honma R, Kinoshita I, Miyoshi E, Tomaru U, Matsuno Y, Shimizu Y, Takeuchi S, Kobayashi Y, Kaga K, Taniguchi N, Dosaka-Akita H
  • Journal Title: Oncology Volume: 88 Issue: 14 Pages: 298-305
  • DOI: 10.18632/oncotarget.3725
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Clec4g (LSECtin) interacts with BACE1 and suppresses Aβ generation (2015)
  • Author(s): Kizuka Y, Kitazume S, Sato K, Taniguchi N
  • Journal Title: FEBS Letters Volume: 589 Issue: 13 Pages: 1418-1422
  • DOI: 10.1016/j.febslet.2015.04.060
  • Peer Reviewed / Open Access
• [Journal Article] Fucosylated surfactant protein-D is a biomarker candidate for the development of chronic obstructive pulmonary disease. (2015)
  • Author(s): Ito E., Oka R., Ishi T., Korekane H., Kurimoto A., Kizuka Y., Kitazume S., Ariki S., Takahashi M., Kuroki Y., Kida K., Taniguchi N.
  • Journal Title: Journal of Proteomics Volume: 127 Pages: 386-394
  • DOI: 10.1016/j.jprot.2015.07.011
  • Peer Reviewed
• [Presentation] グルタチオン研究からシステム糖鎖生物学へ Old sake in a new bottle (2018)
  • Author(s): 谷口直之
  • Organizer: 日本NO学会日本酸化ストレス学会
• [Presentation] 糖鎖研究の目指すもの (2018)
  • Author(s): 谷口直之
  • Organizer: 第65回日本生化学会近畿支部例会
• [Presentation] Systems Glycobiology in Disease and N-glycan Branching (2018)
  • Author(s): Naoyuki Taniguchi
  • Organizer: 24th IUBMB Congress & 15th FAOBMB Congress 2018
  • Int'l Joint Research
• [Presentation] Branching N-glycans in disease: biomarker discovery and therapeutic approach (2018)
  • Author(s): Naoyuki Taniguchi
  • Organizer: The 11th International Symposium on Glycosyltransferases (GlycoT 2018)
  • Int'l Joint Research
• [Presentation] Glycosyltransferases: Structure and Function (2018)
  • Author(s): Naoyuki Taniguchi
  • Organizer: The 11th International Symposium on Glycosyltransferases (GlycoT 2018)
  • Int'l Joint Research
• [Presentation] 糖鎖研究の目指すもの (2018)
  • Author(s): 谷口直之
  • Organizer: オリエンタル酵母長浜研究所研究会
• [Presentation] A unique N-glycan structure, bisecting GIcNAc and Alzheimer's disease (2018)
  • Author(s): Naoyuki Taniguchi
  • Organizer: 15th Meeting of the Asian-Pacific Society for Neurochemistry
  • Int'l Joint Research
• [Presentation] Sugar chains (Glycans) and Cancer (2018)
  • Author(s): 谷口直之
  • Organizer: 第77回日本癌学会学術総会
• [Presentation] 糖鎖と病気の発症、診断、治療 (2018)
  • Author(s): 谷口直之
  • Organizer: 山口大学医学部講義
• [Presentation] コクレチンと補体系について（若宮信隆） (2018)
  • Author(s): 谷口直之
  • Organizer: 第28回日本メイラード学会年会
• [Presentation] Outline of Two-Year Strategic Plan for the HPP (2018)
  • Author(s): Naoyuki Taniguchi
  • Organizer: HUPO 2018
  • Int'l Joint Research
• [Presentation] Nutrient Regulation of Signaling and Gene Expression by O-GIcNAc (Gerald W.Hart) (2018)
  • Author(s): 谷口直之
  • Organizer: 第16回糖鎖科学コンソーシアムシンポジウム
• [Presentation] Branching N-glycans and disease: approach from biochemistry to systems glycobiology (2018)
  • Author(s): Naoyuki Taniguchi
  • Organizer: 2018 Annual Meeting of the Society for Glycobiology
  • Int'l Joint Research
• [Presentation] Branching N-glycans in disease onset, biomarker discovery and therapeutics (2018)
  • Author(s): Naoyuki Taniguchi
  • Organizer: 1st Academic Seminar of IPRC & IGRC
  • Int'l Joint Research / Invited
• [Presentation] Branched N-glycans and their double-edged sword properties in disease (2017)
  • Author(s): Naoyuki Taniguchi
  • Organizer: 19th European Carbohydrate Symposium (EUROCARB)
  • Int'l Joint Research / Invited
• [Presentation] Expression of N-glycan Branching enzymes and their products in Disease implication (2017)
  • Author(s): Naoyuki Taniguchi
  • Organizer: 24th International Symposium on Glycoconjugates (Glyco24)
  • Int'l Joint Research / Invited
• [Presentation] Systems glycobiology in disease and N-glycan branching (2017)
  • Author(s): Naoyuki Taniguchi
  • Organizer: International Symposium“Systems Glycobiology and Beyond”
  • Int'l Joint Research
• [Presentation] Keratan sulfate disaccharides prevent inflammation and emphysema progression in murine lung and its interaction with C-type lectin, langerin (2016)
  • Author(s): Naoyuki Taniguchi
  • Organizer: IUBMB meeting on Frontiers in Glycoscience
  • Place of Presentation: Academia Sinica Taipei（Taiwan）
  • Year and Date: 2016-12-12
  • Int'l Joint Research / Invited
• [Presentation] GlycosylationとRedox 制御のクロストーク (2016)
  • Author(s): 谷口 直之
  • Organizer: 第35回日本糖質学会年会
  • Place of Presentation: 高知市文化プラザ かるぽーと(高知県・高知市)
  • Year and Date: 2016-09-01
  • Invited
• [Presentation] GLYCO-REDOX: NEW SAKE IN AN OLD BOTTLE (2015)
  • Author(s): Naoyuki Taniguchi
  • Organizer: 12th International Symposium on the Maillard Reaction
  • Place of Presentation: 東京大学伊藤国際学術研究センター（東京都・文京区）
  • Year and Date: 2015-09-02
  • Int'l Joint Research / Invited
• [Presentation] 糖鎖、特に分岐型Ｎ－型糖鎖の生理的病態的役割 (2015)
  • Author(s): 谷口直之
  • Organizer: 第38回日本基礎老化学会大会
  • Place of Presentation: パシフィコ横浜（神奈川県・横浜市）
  • Year and Date: 2015-06-14
  • Invited
• [Book] Glycoscience: Basic Science to Applications - Insights from the Japan Consortium for Glycobiology and Glycotechnology - (2019)
  • Author(s): S, Kadomatsu K, Akiyoshi K, Aoki-Kinoshita KF, eds.
  • Total Pages: 337
  • Publisher: Springer Singapore
  • ISBN: 9789811358555
• [Book] ベインズ・ドミニチャク生化学（原書4版） (2018)
  • Author(s): Baynes John W., Dominiczak Marek H, 谷口 直之, 岩井 一宏, 藤井 順逸, 本家 孝一 (担当:共著)
  • Total Pages: 728
  • Publisher: エルゼビア・ジャパン, 丸善出版 (発売)
  • ISBN: 9784621301692
• [Book] Essentials of Glycobiology, 3rd ed. - Ch. 9: N-Glycans (2016)
  • Author(s): Pamela Stanley, Naoyuki Taniguchi and Markus Aebi
  • Publisher: Cold Spring Harbor Laboratory Press
• [Remarks]
  • URL: http://www.riken.jp/research/labs/grc/riken_max_planck/sys_glycobiol/