1997 Fiscal Year Annual Research Report

肝排泄機構におけるリン脂質分子種選択性とその臨床的意義に関する研究

Research Project

Project/Area Number	08670597
Research Institution	HIROSHIMA UNIVERSITY
Principal Investigator	田妻進広島大学, 医学部附属病院, 助手 (80201614)
Keywords	胆汁酸 / 毛細胆管 / 肝内輸送 / リン脂質 / 胆汁分泌 / ヴェジクル / ライポソーム / アシル鎖脂肪酸
Research Abstract	肝は脂質の合成・異化・輸送などの脂質代謝において中心的役割を果たし、その放出経路には血清と胆汁という2方向性がある。肝ミクロソームにおいて種々の酵素による合成過程を経て産生された脂質の一部は、ヴェジクル輸送を介して肝内を移動して毛細胆管膜内層に癒合する。その後、ある種の選択的輸送機構を介して外層へと移動して最終的に胆汁中に分泌されると推定されている。胆汁中脂質の存在様式の物理化学的安定性は脂質担送体の構成リン脂質の疎水性強度に規定され、肝脂質排泄機構におけるリン脂質分子種選択性の制御は、胆道における円滑な胆汁脂質輸送に深く関わっている。本研究では、前年度にリン脂質分子種の疎水性強度の差に基づく肝毛細胆管膜への癒合態度との関わりを、カルシウム沈殿法にて調製したラット肝毛細胆管膜ヴェジクルおよび人工膜ヴェジクル(ライポソーム)を用いて検討し、ライポソームを構成するリン脂質のアシル鎖脂肪酸の不飽和度が癒合性を規定することを解明した。今年度は、胆汁うっ滞状態における肝内脂質ヴェジクルと肝毛細胆管膜の癒合性を検討するとともに、毛細胆管膜上のリン脂質輸送タンパクと推定されている多剤耐性P糖タンパク(mdr2-gene encoding P-glycoprotein)の関わりを検討した。その結果、胆汁うった滞状態では肝内性:肝外性に関わらず、肝毛細胆管膜を構成するリン脂質分子種の疎水性強度は上昇し、人工膜ヴェジクルとの癒合性は低下したが、P糖タンパクの発現には変化を認めなかった。一方、毛細胆管膜中のスフィンゴミエリンの脂肪酸構成がフォスファチジルコリンのそれと鏡面像をなし、両者間の脂肪酸の交換が推定され、膜流動性維持における分子種間連動を示唆した。

Research Products
(10 results)

All Other

All Publications (10 results)

[Publications] Hiroyuki Miura: "Effect of organic anions on acyl chain composition of secreted biliary lecithin in rats : Relation to hepatocellular vesicle pathway." International Hepatology communications. 6. 191-198 (1997)
[Publications] Naomichi Hirano: "Transcytotic vesicle fusion with canalicular membranes is modulated by phospholipid species : Implications for biliary lipid secretion." J Gastroenterology Hepatology. 12. 534-539 (1997)
[Publications] Susumu Tazuma: "A quantitative assessment of serum chylomicron by light scattering intensity : application to the intestinal fat absorption test." J Gastroenterology Hepatology. 12. 713-718 (1997)
[Publications] Hiroyuki Miura: "Effect of cholestasis induced by organic anion on the lipid composition of hepatic membrane subfractions and bile in rats." J Gastroenterology Hepatology. 12. 734-739 (1997)
[Publications] Hiroyuki Miura: "Extracellular and intracellular regulation of biliary lecithin hydrophobicity : relation to organic anion^- or papaverine^- induced uncoupling phenomenon." Digestive Diseases and Science. (in press). (1998)
[Publications] Hiroaki Miyake: "Bile salt hydrophobicity modulates subselection of biliary lecithinspecies in bile salt pool-deplated rats." Digestive Diseases and Science. (in press). (1998)
[Publications] Susumu Tazuma: "Tauroursodeoxycholate and taurochenodeoxycholate stabilize bile lipid metastability through different mechanism : relation to phospholipid fatty acid compositon." Hepatology Research. (in press). (1998)
[Publications] Susumu Tazuma: "A combination therapy of simvastain and ursodeoxycholicacid is more effective on cholesterol gallstone dissolution rates than ursodeoxycholic acid menotherapy." J Clinical Gastroenterology. (in press). (1998)
[Publications] Tomoji Nishioka: "Quantitative assessment on comparative potencies of cholesterol crystal promoting factors : relation to mechanistic characterization." Biochemchal J. (in press). (1998)
[Publications] Susumu Tazuma: "Clinical Studies in Medical Biochemistry" Oxford university Press Inc.(New York). Glew,RH & Ninomiya, Y (2nd eds)., 380 (1997)

1997 Fiscal Year Annual Research Report

肝排泄機構におけるリン脂質分子種選択性とその臨床的意義に関する研究

Principal Investigator

田妻 進 広島大学, 医学部附属病院, 助手 (80201614)

Research Products

[Publications] Hiroyuki Miura: "Effect of organic anions on acyl chain composition of secreted biliary lecithin in rats : Relation to hepatocellular vesicle pathway." International Hepatology communications. 6. 191-198 (1997)

[Publications] Naomichi Hirano: "Transcytotic vesicle fusion with canalicular membranes is modulated by phospholipid species : Implications for biliary lipid secretion." J Gastroenterology Hepatology. 12. 534-539 (1997)

[Publications] Susumu Tazuma: "A quantitative assessment of serum chylomicron by light scattering intensity : application to the intestinal fat absorption test." J Gastroenterology Hepatology. 12. 713-718 (1997)

[Publications] Hiroyuki Miura: "Effect of cholestasis induced by organic anion on the lipid composition of hepatic membrane subfractions and bile in rats." J Gastroenterology Hepatology. 12. 734-739 (1997)

[Publications] Hiroyuki Miura: "Extracellular and intracellular regulation of biliary lecithin hydrophobicity : relation to organic anion^- or papaverine^- induced uncoupling phenomenon." Digestive Diseases and Science. (in press). (1998)

[Publications] Hiroaki Miyake: "Bile salt hydrophobicity modulates subselection of biliary lecithinspecies in bile salt pool-deplated rats." Digestive Diseases and Science. (in press). (1998)

[Publications] Susumu Tazuma: "Tauroursodeoxycholate and taurochenodeoxycholate stabilize bile lipid metastability through different mechanism : relation to phospholipid fatty acid compositon." Hepatology Research. (in press). (1998)

[Publications] Susumu Tazuma: "A combination therapy of simvastain and ursodeoxycholicacid is more effective on cholesterol gallstone dissolution rates than ursodeoxycholic acid menotherapy." J Clinical Gastroenterology. (in press). (1998)

[Publications] Tomoji Nishioka: "Quantitative assessment on comparative potencies of cholesterol crystal promoting factors : relation to mechanistic characterization." Biochemchal J. (in press). (1998)

[Publications] Susumu Tazuma: "Clinical Studies in Medical Biochemistry" Oxford university Press Inc.(New York). Glew,RH & Ninomiya, Y (2nd eds)., 380 (1997)

田妻進広島大学, 医学部附属病院, 助手 (80201614)