Role of Sialic Acid for Angiogenesis

2011 Fiscal Year Final Research Report

• Project/Area Number: 21570154
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: The Institute of Physical and Chemical Research
• Principal Investigator: KAWAGUCHI Shinobu 独立行政法人理化学研究所, 疾患糖鎖研究チーム, 副チームリーダー (80301753)
• Project Period (FY): 2009 – 2011
• Keywords: シアル酸転移酵素 / 血管内皮細胞 / ST6Gal I / PECAM / シアル酸

Research Abstract

In this study, we show thatα2, 6-sialic acid is necessary for the cell-surface residency of platelet endothelial cell adhesion molecule(PECAM), a member of the immunoglobulin superfamily that plays multiple roles in cell adhesion, mechanical stress sensing, antiapoptosis and angiogenesis. As a possible underlying mechanism, we found that the homophilic interactions of PECAM in endothelial cells were dependent onα2, 6-sialic acid. We also found that the absence ofα2, 6-sialic acid downregulated the tyrosine-phosphorylation of PECAM and recruitment of SHP2, and rendered the cells more prone to mitochondria-dependent apoptosis, as evaluated using PECAM-deficient endothelial cells.

Research Products

• [Journal Article] How does N. and O-glycosylation affect the formation and accumulation of Amyloidβ-peptide? (2011)
  • Author(s): S. Kitazume
  • Journal Title: Trends in Glycoscience and Glycotechnology Volume: 23 Pages: 161-167
  • Peer Reviewed
• [Journal Article] Brain-specific expression of N-acetylglucosaminyltransferase IX(GnT-IX) is regulated by epigenetic histone modifications (2011)
  • Author(s): Y. Kizuka, S. Kitazume, M. Yoshida, and N. Taniguchi
  • Journal Title: Biol. Chem. Volume: 286 Pages: 31875-31884
  • Peer Reviewed
• [Journal Article] A unique N-glycan on human transferrin in CSF : a possible biomarker for iNPH (2011)
  • Author(s): S. Futakawa, K. Nara, M. Miyajima, A. Kuno, H. Ito, H. Kaji, K. Shirotani, T. Honda, Y. Tohyama, K. Hoshi, Y. Hanzawa, S. Kitazume, R. Imamaki, K. Furukawa, K. Tasaki, H. Arai, T. Yuasa, M. Abe, H. Arai, H. Narimatsu, and Y. Hashimoto
  • Journal Title: Neurobiol. Aging Volume: (in press)
  • Peer Reviewed
• [Journal Article] Brain endothelial cells produce amyloidβfrom amyloid precursor protein 770 and preferentially secrete the O-glycosylated form (2010)
  • Author(s): S. Kitazume, Y. Tachida, M. Kato, Y. Yamaguchi, T. Honda, Y. Hashimoto, Y. Wada, T. Saito, N. Iwata, T. Saido and N, Taniguchi
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 40097-40103
  • URL: http://www.functionalglycomics.org/fg/update/2010/101111/full/fg.2010.36.shtml
  • Peer Reviewed
• [Journal Article] Simultaneous determination of nucleotide sugars involved in glycosylation with ion-pair reversed. phase HPLC (2010)
  • Author(s): K. Nakajima, S. Kitazume, T. Angata, R. Fujinawa, E. Miyoshi, and N. Taniguchi
  • Journal Title: Glycobiology Volume: 20 Pages: 865-871
  • Peer Reviewed
• [Journal Article] α2, 6-Sialic Acid on Platelet Endotheli al Cell Adhesion Molecule(PECAM) Regulates its homophilic interactio ns and downstream antiapoptotic si gnaling (2010)
  • Author(s): S. Kitazume, R. Imamaki, K. Ogaw a, Y. Komi, S. Futakawa, S. Kojima, Y. Hashimoto, J. D. Marth, J. C. Paulson, and N. Taniguchi
  • Journal Title: J. Biol. Chem. Volume: 285 Pages: 6515-6521
  • URL: http://www.functionalglycomics.org/fg/update/2010/100211/full/fg.2010.8.shtml
  • Peer Reviewed
• [Journal Article] Molecular insights intoβ-galactosideα2, 6-sialyltransferase secretion in vivo (2009)
  • Author(s): S. Kitazume#, R. Oka, K. Ogawa, S. Futakawa, Y. Hagiwara, H. Takigawa, M. Kato, A. Kasahara, E. Miyoshi, N. Taniguchi, and Y. Hashimoto
  • Journal Title: Glycobiology Volume: 19 Pages: 479-487
  • Peer Reviewed
• [Journal Article] Development of sandwich enzyme-linked immunosorbent assay systems for plasmaβ-galactosideα2, 6-sialyltransferase, a possible hepatic disease biomarker (2009)
  • Author(s): S. Futakawa, S. Kitazume, R. Oka, K. Ogawa, Y. A. Kinoshita, K. Miyashita and Y. Hashimoto
  • Journal Title: Analytica Chimica Acta Volume: 531 Pages: 116-120
  • Peer Reviewed
• [Presentation] Brain endothelial cells produce amyloidβfrom amyloid precursor protein 770 and preferentially secrete the O-glycosylated form (2011)
  • Author(s): S. Kitazume
  • Organizer: 第32回日本生化学会シンポジウム
  • Place of Presentation: 京都
  • Year and Date: 2011-09-22
• [Presentation] α2, 6-Sialic Acid on Platelet Endothelial Cell Adhesion Molecule(PECAM) Regulates Its Homophilic Interactions and Downstream Antiapoptotic Signaling (2010)
  • Author(s): S. Kitazume, R. Imamaki, K. Ogawa, Y. Komi, S. Futakawa, S. Kojima, Y. Hashimoto, J. D. Marth, J. C. Paulson, and N. Taniguchi
  • Organizer: ICS2010
  • Place of Presentation: Chiba
  • Year and Date: 2010-08-08
• [Presentation] Brain endothelial cells produce amyloid b from amyloid precursor protein 770 and preferentially secrete the O-glycosylated form (2010)
  • Author(s): S. Kitazume
  • Organizer: Glyco Tokyo 2010
  • Place of Presentation: Tokyo
  • Year and Date: 2010-07-30
• [Presentation] α2, 6-Sialic Acid on Platelet Endothelial Cell Adhesion Molecule(PECAM) Regulates Its Homophilic Interactions and Downstream Antiapoptotic Signaling (2010)
  • Author(s): S. Kitazume
  • Organizer: The 2nd Japan/China Joint Symposium on Glycobiology
  • Place of Presentation: Wako
  • Year and Date: 2010-04-06
• [Presentation] Anα2, 6-Sialic Acid on Platelet Endothelial Cell Adhesion Molecule(PECAM) Regulates Its Homophilic Interactions and Downstream Anti-apoptotic Signaling (2010)
  • Author(s): S. Kitazume
  • Organizer: Joint Japan-CCRC Symposium : New insights into the dynamic functions of glycans
  • Place of Presentation: Athens(U. S. A)
  • Year and Date: 2010-03-05
• [Presentation] Sialic acid-based homophilic PECAM interactions regulate pathological angiogenesis (2009)
  • Author(s): S. Kitazume
  • Organizer: 第32回日本分子生物学会シンポジウム
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-10
• [Presentation] Sialic acid-based homophilic PECAM interactions and pathological angiogenesis (2009)
  • Author(s): Shinobu Kitazume, Rie Imamaki, Kazuko Ogawa, Yusuke Komi, Satoshi Futakawa, Soichi Kojima, Yasuhiro Hashimoto, Jamey D. Marth, James C. Paulson, and Naoyuki Taniguchi
  • Organizer: 2009 Annual Meeting of the Society for Glycobiology
  • Place of Presentation: san Diego
  • Year and Date: 2009-11-14
• [Presentation] 血管新生におけるα2, 6-シアル酸の役割 (2009)
  • Author(s): 北爪しのぶ、今牧理恵、小川加寿子、小見悠介、小嶋聡一、橋本康弘、Jamey D. Marth、谷口直之
  • Organizer: 第29回日本糖質学会
  • Place of Presentation: 飛騨
  • Year and Date: 2009-09-09
• [Book] How does Nand O-glysocylation affect the formation and accumulation of amyloideυ-peptide? (2011)
  • Author(s): Shinobu Kitazume
  • Total Pages: 161-167
• [Book] GnT-IX遺伝子の脳特異的な発現とアイソフォーム「脳21」 (2011)
  • Author(s): 木塚康彦、兼清健志、北爪しのぶ、谷口直之
  • Total Pages: 14, 1, 9-12
• [Book] アルツハイマー病の原因酵素が糖鎖を変えていた、「糖鎖の生物機能の解明と利用技術」 (2009)
  • Author(s): 橋本康弘、北爪しのぶ
• [Patent(Industrial Property Rights)] 認知症診断の為の可溶型アミロイドβ前駆体タンパク質770β切断産物の検出方法 (2011)
  • Inventor(s): 北爪しのぶ、谷口直之、立田由里子、西道隆臣、橋本康弘、本多たかし
  • Industrial Property Rights Holder: 理化学研究所
  • Industrial Property Number: PCT国際特許、PCT/JP2011/067530
  • Filing Date: 2011-07-29
  • Overseas
• [Patent(Industrial Property Rights)] 認知症診断の為の可溶型アミロイドβ前駆体タンパク質770β切断産物の検出方法 (2010)
  • Inventor(s): 北爪しのぶ、谷口直之、立田由里子、西道隆臣、橋本康弘、本多たかし
  • Industrial Property Rights Holder: 理化学研究所
  • Industrial Property Number: 特願、2010-171122
  • Acquisition Date: 2010-07-29