Calcium entry channel related gene expression profiles of endothelial cells by micro-bead array analysis and target gene identification for drug discovery

• Project/Area Number: 18390074
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: WATANABE Hiroshi Hamamatsu University School of Medicine, 医学部, 教授 (50262803)
• Co-Investigator(Kenkyū-buntansha): SATOH Hiroshi 浜松医科大学, 医学部・附属病院, 講師 (30293632) ; KATOH Hideki 浜松医科大学, 医学部, 助教 (80314029) ; MOGAMI Hideo 浜松医科大学, 医学部, 准教授 (90311604)
• Project Period (FY): 2006 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥9,960,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥660,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2006: ¥7,100,000 (Direct Cost: ¥7,100,000)
• Keywords: 循環 / 血管内皮細胞 / カルシウム / ゲノム / 創薬 / 血管内皮細い胞

Research Abstract

血管内皮細胞の機能調節に重要である容量性Ca^(2+)流入経路に関連する遺伝子群を網羅的に解析し、創薬ターゲットとなる候補遺伝子を探索した。容量性Ca^(2+)流入が失活した培養血管内皮細胞系と、容量性Ca^(2+)流入を保持した細胞系を樹立し、差次的発現遺伝子を単離した。最終的には容量性Ca^(2+)流入の有無により効果的に発現差を示す812クローンから99のクラスター(98contigと4cluster-singlet、640ローン)と172クローンのsingletを分離解析に成功した。

Research Products

• [Journal Article] H:Misinterpretation of the effect of amlodipine on cytosolic calcium concentration with fura-2 fluorospectrometry (2008)
  • Author(s): Asai M, Takeuchi K, Uchida S, Urushida T, Katoh H, Satoh H, Yamada S, Hayashi H, Watanabe H
  • Journal Title: Naunyn-Schmiedeberg's Arch Pharmacol 377 Pages: 423-427
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-dependent vasoconstricting factor(s) in remodeled rat femoral arteries (2008)
  • Author(s): Hirao A, Kondo K, Takeuchi K, Inui N, Umemura K, Ohashi K, Watanabe H
  • Journal Title: Cardiovasc Res 79 Pages: 161-168
  • Peer Reviewed
• [Journal Article] 血管内皮細胞とERストレス (2008)
  • Author(s): 渡邉裕司
  • Journal Title: 血管医学 9(4) Pages: 51-57
• [Journal Article] Misinterpretation of the effect of amlodipine on cytosolic calcium concentration with fura-2 fluorospectrometry (2008)
  • Author(s): Asai M, Takeuchi K, Uchida S, Urushida T, Katoh H, Satoh H, Yamada S, Hayashi H, Watanabe H
  • Journal Title: Naunyn-Schiniedeberg's Arch Pharmacol 377 Pages: 423-427
  • Peer Reviewed
• [Journal Article] Extracellular acidosis suppresses endothelial function by inhibiting store-operated Ca^<2+> entry via non-selective cation channels
  • Author(s): Asai M, Takeuchi K, Saotome M, Urushida T, Katoh H, Satoh H, Hayashi H, Watanabe H
  • Journal Title: Cardiovasc Res (in press)
  • Peer Reviewed
• [Journal Article] Extracellular acidosis suppresses endothelial function by inhibiting store-operated Ca^<2+> entry via non-selective cation channels Corresponding Author
  • Author(s): Asai M, Takeuchi K, Saotome M, Urushida T, Katoh H, Satoh H, Hayashi H, Watanabe H
  • Journal Title: Cardiovasc Res (in press)
  • Peer Reviewed
• [Presentation] Omega-6 Ployunsaturated Fatty Acids, Arachidonic and Linoleic Acids, but not Other Free Fatty Acids, Suppress Endothelial Calcium Signaling and Functions (2009)
  • Author(s): Takeuchi K, Watanabe H
  • Organizer: The73st Annual Scientific Meeting the Japanese Circulation Society/ P
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] H:Regenerated Endothelium Produces not Vasodilative but Vasoconstrictive Prostanoid(s) via Cyclooxygenase - dependent Pathway (2008)
  • Author(s): Takeuchi K , Hirao A, Iida K, Ohashi K, Watanabe H
  • Organizer: The72st Annual Scientific Meeting the Japanese Circulation Society
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-29
• [Presentation] Free Fatty Acids (FFAs), Arachidonic and Linoleic Acids but not other FFAs, Suppress Endothelial Function by lnhibiting Endothelial Ca2+ Responses (2008)
  • Author(s): Takeuchi K , Iida K, Watanabe H
  • Organizer: The72st Annual Scientific Meeting the Japanese Circulation Society/P
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Extracellular but not Intracellular Acidosis Suppresses Endothelial Function by nhibiting Intracellular Calcium Responses (2008)
  • Author(s): Asai M, Takeuchi K, Urushida T, Katou H, Satoh H, Hayashi H, Watanabe H
  • Organizer: The72st Annual Scientific Meeting the Japanese Circulation Society/P
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Extracellular but not Intracellular Acidosis Suppresses Endothelial Function by Inkibiting Intracellular Calcium Responses (2008)
  • Author(s): Alai M, Takeuchi K, Urushida T, Katou H, Satoh H, Hayashi H, Watanabe H
  • Organizer: The 72st Annual Scientific Meeting the Japanese Circulation Society/P
  • Place of Presentation: 福岡
  • Year and Date: 2008-03-28
• [Presentation] Endothelial Ca^<2+>-Control in health and disease (2008)
  • Author(s): Watanabe H
  • Organizer: 74th Anllual Meeting of the German Cardiac Society
  • Place of Presentation: Mannheim
  • Year and Date: 2008-03-27
• [Presentation] Protease-activated receptor(PAR)を介する血管内皮細胞内カルシウム応答に対するブラジキニン(BK)およびBK受容体拮抗薬の作用 (2007)
  • Author(s): 竹内和彦,内海明子,乾直輝,渡邉裕司
  • Organizer: 第28回日本臨床薬理学会年会/P
  • Place of Presentation: 栃木
  • Year and Date: 2007-11-29
• [Presentation] H : Biomarkers in cardiovascular diseases : A new tool to evaluate endothelial function (2007)
  • Author(s): Takeuchi K, Utsumi A, Inui N, Watanabe H
  • Organizer: The 3rd China-Japan Joint Meeting of Basic and Clinical Pharmacology/P
  • Place of Presentation: Dalian(China)
  • Year and Date: 2007-08-23
• [Presentation] Direct Effect of ACE Inhibitors on Endothelium : ACE Inhibitors Enhance Kallikrein-induced Ca2+ Responses via Endogenous Bradykinin Endothelial Cells (2007)
  • Author(s): Takeuchi K, Watanabe H
  • Organizer: The71st Annual Scientific Meeting the Japanese Circulation Society/P
  • Place of Presentation: 神戸
  • Year and Date: 2007-03-17
• [Presentation] Antiproliferative Effect of Cyclic AMP on Human Umbilical Vein Endothelial Cells through TGF-beta Inducing p21 (Cip1/Waf1) Expression (2007)
  • Author(s): Takeuchi K, Yang Yingbao,Watanabe H
  • Organizer: The71st Annual Scientific Meeting the Japanese Circulation Society/P
  • Place of Presentation: 神戸
  • Year and Date: 2007-03-17
• [Presentation] カリクレイン誘導性血管内皮細胞内カルシウム応答に対するACE阻害薬の作用 (2006)
  • Author(s): 竹内和彦,渡邉裕司
  • Organizer: 第27回日本臨床薬理学会年会/P
  • Place of Presentation: 東京
  • Year and Date: 2006-11-30
• [Presentation] Regenerated endothelial cells produce vasoconstrictive prostanoid(s) rather than vasodilative prostanoid(s) through COX-1 and COX-2 dependent pathways (2006)
  • Author(s): Hirao A, Kondo K, Takeuchi K, Umemura K, Watanabe H
  • Organizer: The 79th Scientific Sessions of American Heart Association
  • Place of Presentation: Chicago(USA)
  • Year and Date: 2006-11-14
• [Presentation] Assessment of Posture- Related Dynamic Changes in Cerebral Blood Flow Using Near-Infrared Time- Resolved Spectroscopy : A New Tool To Evaluate Effects of Antihypertensives on Cerebral Circulation (2006)
  • Author(s): Takeuchi K, Nakamura R, Kageyama M, Watanabe H
  • Organizer: The 79th Scientific Sessions of American Heart Association
  • Place of Presentation: Chicago(USA)
  • Year and Date: 2006-11-13
• [Presentation] カリクレインによる血管内皮細胞内カルシウム応答の変化の検討 (2006)
  • Author(s): 竹内和彦, 中村玲子, 影山美智代, 平尾晃子, 渡邉裕司
  • Organizer: 日本循環器学会第128回東海・第113回北陸合同地方会
  • Place of Presentation: 名古屋
  • Year and Date: 2006-11-05
• [Book] AHA Highlights 2007, Cardiovascular Pharmacogenomics : Advances and Challenges in Personalized Medicine (2007)
  • Author(s): 渡邉裕司
  • Publisher: 協和企画
• [Book] The Vascular Endothelium I Calcium Signalling in the Endothelium (2006)
  • Author(s): Tran QK, Watanabe H
  • Publisher: Springer,Handbook of Experimental Pharmacology
• [Remarks]
  • URL: http://www2.hama-med.ac.jp/w1b/cpharm/clinpharm.html
• [Remarks]
  • URL: http://www2.hama-med.ac.jp/wlb/cpharm/clinpharm.html
• [Remarks]
  • URL: http://www2.hama-med.ac.jp/w1b/cpharm/clinpharm.html