Role of Sialic Acid for Angiogenesis

• 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
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: シアル酸転移酵素 / 血管内皮細胞 / ST6Gal I / PECAM / シアル酸 / α2,6-シアル酸 / アポトーシス / SHP2 / 接着分子 / 血管新生 / ITIM

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-specific expression of N-acetylglucosaminyltransferase IX (GnT-IX) is regulated by epigenetic histone modifications (2011)
  • Author(s): Y.Kizuka, S.Kitazume, M.Yoshida, N.Taniguchi
  • Journal Title: J.Biol.Chem. Volume: 286 Issue: 36 Pages: 31875-31884
  • DOI: 10.1074/jbc.m111.251173
  • 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] Brain endothelial cells produce amyloid β from 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, N, Taniguchi
  • Journal Title: J.Biol.Chem. Volume: 285 Pages: 40097-40103
  • 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, N.Taniguchi
  • Journal Title: Glycobiology Volume: 20 Pages: 865-871
  • Peer Reviewed
• [Journal Article] 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, N.Taniguchi
  • Journal Title: J.Biol.Chem Volume: 285 Pages: 6515-6521
  • Peer Reviewed
• [Journal Article] 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, N.Taniguchi
  • Journal Title: J.Biol.Chem. 285(In press)
  • 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
• [Journal Article] Molecular insights into β-galactoside α2, 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, Y.Hashimoto
  • Journal Title: Glycobiology 19 Pages: 479-487
  • Peer Reviewed
• [Journal Article] Development of sandwich enzyme-linked immunosorbent assay systems for plasma β-galactoside α2, 6-sialyltransferase, a possible hepatic disease biomarker (2009)
  • Author(s): S.Futakawa, S.Kitazume, R.Oka, K.Ogawa, Y.A.Kinoshita, K.Miyashita, Y.Hashimoto
  • Journal Title: Analytica Chimica Acta 531 Pages: 116-120
  • Peer Reviewed
• [Journal Article] Integrated approach toward the discovery of glyco-biomarkers of in flammation-related diseases
  • Author(s): Takashi Angata, Reiko Fujinawa, Ayako Kurimoto, Kazuki Nakajima, Masaki Kato, Shinji Takamatsu, Hiroaki Korekane, Cong-Xiao Gao, Kazuaki Ohtsubo, Shinobu Kitazume, Naoyuki Taniguchi
  • Journal Title: Annals of New York Academy of Sciences Volume: (In press)
  • Peer Reviewed
• [Journal Article] High Throughput ELISAs to Measure a Unique Glycan on Transferrin in Cerebrospinal Fluid : A Possible Extension toward Alzheimer's Disease Biomarker Development
  • Author(s): K.Shirotani, S.Futakawa, K.Nara, K.Hoshi, T.Saito, Y.Tohyama, S.Kitazume, T.Yuasa, M.Miyajima, H, Arai, A.Kuno, H.Narimatsu, Y.Hashimoto
  • Journal Title: International Journal of Alzheimer's Disease Volume: (In press)
  • 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] Brain endothelial cells produce amyloid β from amyloid precursor protein 770 and preferentially secrete the O-glycosylated form (2011)
  • Author(s): Shinobu Kitazume
  • Organizer: 第32回日本生化学会シンポジウム
  • Place of Presentation: 京都(招待講演)
  • 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] 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, N.Taniguchi
  • Organizer: ICS2010
  • Place of Presentation: 千葉県・幕張
  • 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] Brain endothelial cells produce amyloid β from amyloid precursor protein 770 and preferentially secrete the O-glycosylated form (2010)
  • Author(s): Shinobu Kitazume
  • Organizer: GlycoT2010
  • Place of Presentation: 東京都・浅草
  • 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 regulate pathological angiogenesis (2009)
  • Author(s): 北爪しのぶ
  • Organizer: 第32回日本分子生物学会
  • Place of Presentation: パシフィコ横浜(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
• [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・世界生活文化センター(岐阜)
  • 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
• [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
• [Book] 「脳21」GnT-IX遺伝子の脳特異的な発現とアイソフォーム (2011)
  • Author(s): 木塚康彦、兼清健志、北爪しのぶ、谷口直之
  • Total Pages: 85
  • Publisher: メディカルオンライン
• [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
• [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
  • Total Pages: 12
  • Publisher: 蛋白質・核酸・酵素
• [Remarks]
  • URL: http://www.functionalglycomics.org/fg/update/2010/100211/full/fg.2010.8.shtml
• [Remarks]
  • URL: http://www.functionalglycomics.org/fg/update/2010/100211/full/fg.2010.8.shtml
• [Remarks]
  • URL: http://www.functionalglycomics.org/fg/archive/2010/11/fa.shtml
• [Remarks]
  • URL: http://www.riken.go.jp/r-world/research/results/2010/100302/index.html
• [Remarks]
  • URL: http://www.riken.go.jp/r-world/research/results/2010/101021/index.html
• [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
  • 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770'β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
  • 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 (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: 独立行政法人理化学研究所
  • Industrial Property Number: 2010-171122
  • Filing Date: 2011-07-29
• [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
  • Acquisition Date: 2010-07-29