Role of selectin-carbohydrate interactions in rolling of cells in blood vessels of the brain

• Project/Area Number: 22790303
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General medical chemistry
• Research Institution: Nagoya University (2011); National Center for Geriatrics and Gerontology (2010)
• Principal Investigator: UCHIMURA Kenji 名古屋大学, 医学系研究科, 特任准教授 (20450835)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 細胞・組織 / 生体分子 / 糖鎖 / 脳・神経

Research Abstract

It has been reported that bone marrow derived cells extravasate into the brain of Alzheimer model mice. Molecular interactions between selectins and their carbohydrate ligands are the first step of leukocyte infiltration into tissues through the blood. Here, we investigated possible involvement of selectins and their ligands in diapedesis of bone marrow derived cells into Alzheimer brain. We have detected cell surface expression of sialyl Lewis X, a ligand of selectins, ina mouse bone marrow cell line. We also found that expression of one of selectins was up-regulated in brain vasculature of aged Alzheimer model mice. We have shown that the selectin ligand was involved in rolling and adhesion of bone marrow cells in the brain of Alzheimer model mice. These results indicated that selectin-carbohydrate ligandinteraction might be important for extravasation of bone marrow derived cells into Alzheimer brain.

Research Products

• [Journal Article] Expression of long-form N-acetylglucosamine-6- O-sulfotransferase 1 in human high endothelial venules (2012)
  • Author(s): Fujiwara, M., Kobayashi, M., Hoshino, H., Uchimura, K., Nakada, T., Masumoto, J., Sakai, Y., Fukuda, M., Nakayama, J
  • Journal Title: J. Histochem. Cytochem Volume: 60 Pages: 397-407
  • NAID: 120007110481
  • Peer Reviewed
• [Journal Article] Heparan sulfate subdomains that are degraded by Sulf accumulate in cerebral amyloid β plaques of Alzheimer's disease: evidence from mouse models and patients (2012)
  • Author(s): Hosono-Fukao, T., Ohtake-Niimi, S., Hoshino, H., Britschgi, M., Akatsu, H., Hossain, M. M., Nishitsuji, K., van Kuppevelt, T. H., Kimata, K., Michikawa, M. Wyss-Coray, T., and Uchimura, K.
  • Journal Title: Am. J. Pathol Volume: 180 Pages: 2056-2067
  • Peer Reviewed
• [Journal Article] Expression of long-form N-acetylglucosamine-6-0-sulfo-transferase1in human high endothelial venules (2012)
  • Author(s): Fujiwara M, KobayashiM, Hoshino H, Uchimura K, NakadaT, Masumoto J, Sakai Y, Fukuda M, Nakayama J
  • Journal Title: J Histochem Cytochem Volume: 60 Issue: 5 Pages: 397-407
  • DOI: 10.1369/0022155412437613
  • Peer Reviewed
• [Journal Article] RB4CD12 epitope expression and heparan sulfate disaccharide composition in brain vasculature (2011)
  • Author(s): Hosono-Fukao, T., Ohtake-Niimi, S., Nishitsuji, K., Hossain, M. M., van Kuppevelt, T. H., Michikawa, M. and Uchimura, K.
  • Journal Title: J. Neurosci. Res Volume: 89 Pages: 1840-1848
  • Peer Reviewed
• [Journal Article] Lipoprotein lipase is a novel Abeta-binding protein that promotes glycosaminoglycan-dependent cellular uptake of Abeta in astrocytes (2011)
  • Author(s): Nishitsuji, K., Hosono, T., Uchimura, K. and Michikawa, M
  • Journal Title: J. Biol. Chem Volume: 286 Pages: 6393-6401
  • Peer Reviewed
• [Journal Article] extracellular endosulfatases that regulate physiological functions of heparan sulfate (2011)
  • Author(s): Uchimura, K
  • Journal Title: 生化学 Volume: 83 Pages: 216-223
  • Peer Reviewed
• [Journal Article] RB4CD12 epitope expression and heparan sulfate disaccharide composition in brain vasculature (2011)
  • Author(s): Hosono-Fukao, T, et al
  • Journal Title: J.Neurosci.Res Volume: 89 Issue: 11 Pages: 1840-1848
  • DOI: 10.1002/jnr.22690
  • Peer Reviewed
• [Journal Article] Lipoprotein lipase is a novel amyloid beta (Abeta)-binding protein that promotes glycosaminoglycan-dependent cellular uptake of Abeta in astrocytes (2011)
  • Author(s): Nishitsuji, et al
  • Journal Title: J Biol Chem Volume: 286 Pages: 6393-6401
  • Peer Reviewed
• [Journal Article] Use of a phage display antibody to measure the enzymatic activity of the Sulfs (2010)
  • Author(s): Uchimura, K., Lemjabbar-Alaoui, H., van Kuppevelt, T. H. and Rosen, S. D
  • Journal Title: Methods Enzymol Volume: 480 Pages: 51-64
  • Peer Reviewed
• [Presentation] Keratan sulfate: development and pathology (2012)
  • Author(s): Kenji Uchimura
  • Organizer: IBMS Glycobiology meeting
  • Place of Presentation: Taiwan
  • Year and Date: 2012-01-10
• [Presentation] アルツハイマー病モデルマウス脳に発現する細胞外マトリックスコンドロイチン硫酸糖鎖の構造解析 (2011)
  • Author(s): 新美しおり, 星野瞳, 細野友美,道川誠, 内村健治
  • Organizer: 第30回日本認知症学会
  • Place of Presentation: 東京
  • Year and Date: 2011-11-12
• [Presentation] Sulfotransferases that regulate expression of the 5D4 keratan sulfate epitope in early postnatal mouse brain Hitomi Hoshino (2011)
  • Author(s): Shiori Ohtake-Niimi, Makoto Michikawa, Reiji Kannagi, and Kenji Uchimura
  • Organizer: Annual meeting of Glycobiology 2011
  • Place of Presentation: Seattle, USA
  • Year and Date: 2011-11-11
• [Presentation] Cahbohydrate-protein interactions in the vasculature (2011)
  • Author(s): Kenji Uchimura
  • Organizer: IBMS Seminar, Academia Sinica
  • Place of Presentation: Taiwan
  • Year and Date: 2011-10-17
• [Presentation] セレクチンリガンド形成に関わる硫酸転移酵素は生後マウス発達脳における 5D4ケラタン硫酸糖鎖抗原の発現を制御する 星野瞳 (2011)
  • Author(s): 道川誠, 神奈木玲児, 内村健治
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] アルツハイマー病モデルマウス脳に発現するコンドロイチン硫酸グリコサミノグリカンの構造解析 (2011)
  • Author(s): 新美しおり, 星野瞳, 道川誠, 門松健治, 内村健治
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
  • Year and Date: 2011-09-23
• [Presentation] セレクチンリガンド形成に関わる硫酸転移酵素は生後マウス発達脳における5D4ケラタン硫酸糖鎖抗原の発現を制御する (2011)
  • Author(s): 星野瞳 他４名
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Sulfotransferases that regulate expression of the 5D4 keratan sulfate epitope in early postnatal mouse brain (2011)
  • Author(s): Hitomi Hoshino et al
  • Organizer: Annual meeting of Glycobiology 2011
  • Place of Presentation: Seattle, USA
• [Presentation] アルツハイマー病モデルマウス大脳皮質に発現するヘパラン硫酸グリコサミノグリカンの構造解析 (2010)
  • Author(s): 細野友美, 新美しおり, ホサインモタラブ, 菅谷典子, 赤津裕康, トニーワイスコレイ, 木全弘治, 道川誠, 内村健治
  • Organizer: 第83回日本生化学会大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-09
• [Presentation] Immunolocalization of the RB4CD12 Anti-Heparan Sulfate Epitope in Brain Microvessels and Its Degradation by Sulf-1 and Sulf-2 (2010)
  • Author(s): Hosono-Fukao T, Hossain M, Ohtake-Niimi S , van Kuppevelt T, Michikawa M, Rosen S and Uchimura K
  • Organizer: Annual meeting of Glycobiology 2010
  • Place of Presentation: St. Pete Beach, USA
  • Year and Date: 2010-11-08
• [Presentation] アルツハイマー病モデルマウス脳内に発現するヘパラン硫酸糖鎖の内部ドメイン構造の解析 (2010)
  • Author(s): 細野友美, 新美しおり, モタラブホサイン, マーカスブリッチギ, 赤津裕康, 菅谷典子, 木全弘治, 道川誠, トニーワイスコレイ, 内村健治
  • Organizer: 第29回日本認知症学会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-11-05
• [Presentation] Immunolocalization of the RB4CD12 anti-heparan sulfate epitope in the brain and its degradation by Sulfs, extracellular endosulfatases (2010)
  • Author(s): Hossain M, Hosono T, Niimi S, van Kuppevelt T, Michikawa M, Rosen S, Uchimura K.
  • Organizer: 25th International Carbohydrate Symposium (ICS2010) Makuhari Messe
  • Place of Presentation: Makuhari
  • Year and Date: 2010-08-05
• [Presentation] Immunolocalization of the RB4CD12 anti-heparan sulfate epitope in the brain and its degradation by Sulfs, extracellular endosulfatases (2010)
  • Author(s): Hossain, et al
  • Organizer: 25th International Carbohydrate Symposium (ICS2010)
  • Place of Presentation: 幕張
  • Year and Date: 2010-08-05
• [Presentation] The Sulf-degrading heparan sulfate epitope accumulates in cerebral amyloid β plaques of mouse models and patients of Alzheimer's disease (2010)
  • Author(s): Hosono T, Hossain M, Britschgi M, Akatsu H, van Kuppevelt T, Michikawa M,Wyss-Coray T, Uchimura K.
  • Organizer: 25th International Carbohydrate Symposium (ICS2010) Makuhari Messe
  • Place of Presentation: Makuhari
  • Year and Date: 2010-08-02
• [Presentation] The Sulf-degrading heparan sulfate epitope accumulates in cerebral amyloid β plaques of mouse models and patients of Alzheimer's disease (2010)
  • Author(s): Hosono, et al
  • Organizer: 25th International Carbohydrate Symposium (ICS2010)
  • Place of Presentation: 幕張
  • Year and Date: 2010-08-02
• [Remarks]
  • URL: http://www.med.nagoya-u.ac.jp/biochem/index.html
• [Remarks] HP アドレス
  • URL: http://www.med.nagoya-u.ac.jp/biochem/index.html