Role of the G-protein-coupled receptors that sense an extracellular pH-stress in arteriosclerotic functions of vascular cells

• Project/Area Number: 19591034
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Gunma University
• Principal Investigator: TOMURA Hideaki Gunma University, 生体調節研究所, 准教授 (70217553)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 細胞・組織 / シグナル伝達 / 生理活性 / pH / G蛋白連関型受容体

Research Abstract

正常の血管内膜のpHは7.7前後であるが、動脈硬化症のリピドリッチな部位ではpHが7.1程度まで低下する。細胞外pHの低下は血管を構成する細胞の種々の機能を変化させるがその実体は不明である。本研究では「OGR1ファミリーが、pHセンサーとして機能し、動脈硬化症と関連した血管機能の制御に関与している」との仮説のもとに実験を行った。その結果、この受容体ファミリーが、動脈硬化に関係する種々の血管細胞機能を調節していることを明らかにした。

Research Products

• [Journal Article] Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages (2009)
  • Author(s): Mogi C, Tobo M, Tomura H, Murata N, He XD, Sato K, Kimura T, Ishizuka T, Sasaki T, Sato T, Kihara Y, Ishii S, Harada A, and Okajima F
  • Journal Title: J Immunol 182 Pages: 3243-51
  • Peer Reviewed
• [Journal Article] LPA1 receptors mediate stimulation, whereas LPA2 receptors mediate inhibition, of migration of pancreatic cancer cells in response to lysophosphatidic acid and malignant ascites (2009)
  • Author(s): Komachi M, *Tomura H, Malchinkhuu E, Tobo M, Mogi C, Yamada T, Kimura T, Kuwabara A, Ohta H, Im DS, Kurose H, Takeyoshi I, Sato K, and Okajima F
  • Journal Title: Carcinogenesis 30 Pages: 457-65
  • Peer Reviewed
• [Journal Article] Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients. (2009)
  • Author(s): Enya, M., et al.
  • Journal Title: Hum Mutat 29
  • Peer Reviewed
• [Journal Article] LPA1 receptors mediate stimulation, whereas LPA2 receptors mediate inhibition, of migration of pancreatic cancer cells in response to lysophosphatidic acid and malignant ascites. (2009)
  • Author(s): Komachi, M., et al.
  • Journal Title: Carcinogenesis 30 Pages: 457-465
  • Peer Reviewed
• [Journal Article] Involvement of proton-sensing TDAG8 in extracellular acidification-induced inhibition of proinflammatory cytokine production in peritoneal macrophages. (2009)
  • Author(s): Mogi, C., et al.
  • Journal Title: J Immunol 182 Pages: 3243-3251
  • Peer Reviewed
• [Journal Article] Induction of scavenger receptor class B type I is critical for simvastatin enhancement of high-density lipoprotein-induced anti-inflammatory actions in endothelial cells (2008)
  • Author(s): Kimura T, Mogi C, Tomura H, kuwabara A, Im DS, Sato K, Kurose H, Murakami M, and Okajima F
  • Journal Title: J Immunol 181 Pages: 7332-40
  • Peer Reviewed
• [Journal Article] Stimulatory role of lysophosphatidic acid in cyclooxygenase-2 induction by synovial fluid of patients with rheumatoid arthritis in fibroblast-like synovial cells (2008)
  • Author(s): Nochi H, Tomura H, Tobo M, Tanaka N, Sato K, Shinozaki T, Kobayashi T, Takagishi K, Ohta H, Okajima F, and Tamoto K
  • Journal Title: J Immunol 181 Pages: 5111-9
  • Peer Reviewed
• [Journal Article] Mutations in the small heterodimer partner gene increase morbidity risk in Japanese type 2 diabetes patients (2008)
  • Author(s): Enya M, Horikawa Y, Kuroda E, Yonemaru K, Tonooka N, Tomura H, Oda N, Yokoi N, Yamagata K, Shihara N, Iizuka K, Saibara T, Seino S, and Takeda J
  • Journal Title: Hum Mutat 29
  • Peer Reviewed
• [Journal Article] N,N-Dimethyl-D-erythro-sphingosine inhibits store-operated Ca2+ entry in U937 monocytes (2008)
  • Author(s): Jo JY, Kim HL, Lee YK, Tomura H, Bae YS, Okajima F, and Im DS
  • Journal Title: J Pharmacol Sci 107 Pages: 303-7
  • NAID: 10024321429
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 Expression and Prostaglandin E2 Production in Response to Acidic pH Through OGR1 in A Human Osteoblastic Cell Line (2008)
  • Author(s): Tomura H, Wang JQ, Liu Jp, Komachi M, Damirin A, Mogi C, Tobo M, Nochi H, Tamoto K, Im DS, Sato K, and Okajima F
  • Journal Title: J Bone Miner Res 23 Pages: 1129-39
  • Peer Reviewed
• [Journal Article] (2008)
  • Author(s): Malchinkhuu E, Sato K, Maehama T, Mogi C, Tomura H, Ishiuchi S, Yoshimoto Y, Kurose H, and Okajima F
  • Journal Title: 366 Pages: 963-8
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 expression and prostaglandin E2 production in response to acidic pH through OGR1 in a human osteoblastic cell line. (2008)
  • Author(s): Tomura, H., et al.
  • Journal Title: J Bone Miner Res 23 Pages: 1129-1139
  • Peer Reviewed
• [Journal Article] N,N-Dimethyl-D-erythro-sphingosine inhibits store-opera ted Ca2+ entry in U937 monocytes. (2008)
  • Author(s): Jo, JY., et al.
  • Journal Title: J Pharmacol Sci 107 Pages: 303-307
  • Peer Reviewed
• [Journal Article] Stimulatory role of lysophosphatidic acid in cyclooxygenase-2 induction by synovial fluid of patients with rheumatoid arthritis in fibroblast-like synovial cells. (2008)
  • Author(s): Nochi, H., et al.
  • Journal Title: J Immunol 181 Pages: 5111-5119
  • Peer Reviewed
• [Journal Article] Induction of scavenger receptor class B type I is critical for simvastatin enhancement of high-density lipoprotein-induced anti-inflammatory actionsin endothelial cells. (2008)
  • Author(s): Kimura, T., et al.
  • Journal Title: J Immunol 181 Pages: 7332-7340
  • Peer Reviewed
• [Journal Article] Cyclooxygenase-2 Expression and Prostaglandin E2 Production Response to Acidic pH Through OGR1 in AHuman Osteoblastic Cell Line (2008)
  • Author(s): Tomura, H., et. al.
  • Journal Title: J Bone Miner Res (In press)
  • Peer Reviewed
• [Journal Article] S1P(2) receptors mediate inhibition of glioma cell migration through Rho signaling pathways independent of PTEN (2007)
  • Author(s): Sato K, Malchinkhuu E, Horiuchi Y, Mogi C, Tomura H, Tosaka M, Yoshimoto Y, Kuwabara A, and Okajima F
  • Journal Title: Biochem Biophys Res Commun 103 Pages: 2610-19
  • Peer Reviewed
• [Journal Article] Critical role of ABCA1 transporter in sphingosine 1-phosphate release from astrocytes (2007)
  • Author(s): Sato K, Malchinkhuu E, Horiuchi Y, Mogi C, Tomura H, Tosaka M, Yoshimoto Y, Kuwabara A, and Okajima F
  • Journal Title: J Neurochem 359 Pages: 649-54
  • Peer Reviewed
• [Journal Article] HDL-like lipoproteins in cerebrospinal fluid affect neural cell activity through lipoprotein-associated sphingosine 1-phosphate (2007)
  • Author(s): Tobo M, Tomura H, Mogi C, Wang JQ, Liu JP, Komachi M, Damirin A, Kimura T, Murata N, Kurose H, Sato K, and Okajima. F
  • Journal Title: Biochem Biophys Res Commun 19 Pages: 1745-53
  • Peer Reviewed
• [Journal Article] Role of lipoprotein-associated lysophospholipids in migratory activity of coronary artery smooth muscle cells (2007)
  • Author(s): Damirin A, Tomura H, Komachi M, Liu JP, Mogi C, Tobo M, Wang JQ, Kimura T, Kuwabara A, Yamazaki Y, Ohta H, Im DS, Sato K, and Okajima F
  • Journal Title: Am J Physiol Heart Circ Physiol 292
• [Journal Article] Cloning and expression of vacuolar proton-pumping ATPase subunits in the follicular epithelium of the bullfrog endolymphatic sac (2007)
  • Author(s): Yajima S, Kubota M, Nakakura T, Hasegawa T, Katagiri N, Tomura H, Sasayama Y, Suzuki M, and Tanaka S
  • Journal Title: Zoolog Sci 24 Pages: 147-57
  • NAID: 130000016955
  • Peer Reviewed
• [Journal Article] HSF1 and constitutively active HSF1 improve vascular endothelial function (heat shock proteins improve vascular endothelial function) (2007)
  • Author(s): Uchiyama T, Atsuta H, Utsugi T, Oguri M, Hasegawa A, Nakamura T, Nakai A, Nakata M, Maruyama I, Tomura H, Okajima F, Tomono S, Kawazu S, Nagai R, and Kurabayashi M
  • Journal Title: Atherosclerosis 190 Pages: 321-9
  • Peer Reviewed
• [Journal Article] Previously postulated "ligand-independent"signaling of GPR4 is mediated through proton-sensing mechanisms (2007)
  • Author(s): Tobo, M., et. al.
  • Journal Title: Cell Signal 19 Pages: 1745-1753
  • Peer Reviewed
• [Journal Article] Role of lipoprotein-associated lysophospholipids in migratory activity of coronary artery smooth muscle cells (2007)
  • Author(s): Damirin, A., et. al.
  • Journal Title: Am J Physiol Heart Circ Physiol 292
  • Peer Reviewed
• [Presentation] 岡島史和「細胞外pHの低下に伴うヒト気管支平滑筋細胞からのインターロイキン6の産生は、OGR1受容体を介して引き起こされる」 (2008)
  • Author(s): 戸村秀明、一文字功、石塚全、小町麻由美、当房雅之、佐藤幸市、茂木千尋、森昌朋
  • Organizer: 第31回日本分子生物学会・第81回日本生化学会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] 細胞外pHの低下に伴うヒト気管支平滑筋細胞からのインターロイキン6の産生は、OGR1受容体を介して引き起こされる (2008)
  • Author(s): 戸村秀明他
  • Organizer: 第31回日本分子隼物学会 第81回日本生化学会合同大会
  • Place of Presentation: 神戸ポートアイランド(兵庫県、神戸)
  • Year and Date: 2008-12-11
• [Presentation] 岡島史和「ヒト骨芽細胞における細胞外pHの低下に伴うCOX-2発現誘導・PGE2産生とOGR1受容体の関連解析」 (2008)
  • Author(s): 戸村秀明、劉進朋、当房雅之、Doon-Soon Im、茂木千尋
  • Organizer: 第50回日本脂質生化学会
  • Place of Presentation: 徳島
  • Year and Date: 2008-06-05
• [Presentation] Acidic pH Induced Cyclooxygenase-2 Expression and Prostaglandin E2 Production through Ovarian cancer G-protein-coupled receptor 1 (OGR1) in Human Osteoblasts (2007)
  • Author(s): Hideaki Tomura, Jin-peng Liu, Mayumi Komachi, Wang Ju Qiang, Masayuki Tobo, Hiromi Nochi, Koichi Tamoto, Alatangaole Damirin, Koichi Sato, Chihiro Mogi, and Fumikazu Okajima
  • Organizer: 第30回日本分子生物学会・第80回日本生化学会合同大会
  • Place of Presentation: 横浜
  • Year and Date: 2007-12-14
• [Presentation] 岡島史和「細胞外pHを関知するG蛋白連関型受容体の細胞内情報伝達機構」 (2007)
  • Author(s): 戸村秀明、当房雅之、茂木千尋
  • Organizer: 第32回日本比較内分泌学会
  • Place of Presentation: 日光
• [Presentation] 細胞外pHを感知するG蛋白連関型受容体の細胞内情報伝達機構 (2007)
  • Author(s): 戸村 秀明, 他
  • Organizer: 第32回比較内分泌学会大会
  • Place of Presentation: 日光プリンスホテル(栃木県、日光)
• [Remarks] ホームページ等アドレス
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