1996 年度実績報告書

動脈硬化発症、進展の病態に関する分子生物学的研究

研究課題

研究課題/領域番号	08407026
研究種目	基盤研究(A)
研究機関	京都大学
研究代表者	北徹京都大学, 医学研究科, 教授 (60161460)
研究分担者	石井賢二京都大学, 医学研究科, 助手 (00212811) 若月芳雄京都大学, 医学研究科, 講師 (40220826) 横出正之京都大学, 医学研究科, 講師 (20252447) 土井俊夫京都大学, 医学研究科, 講師 (60183498) 村上元庸京都大学, 医学研究科, 助教授 (10157761)
キーワード	血管内皮細胞 / リゾフォスファチジルコリン / HB-EGF / PECAM-1 / JNK / ERK / Tリンパ球 / IFN-γ
研究概要	血管内皮細胞のLyso-PCによる活性化の分子機構について、BAECを主に用いて検討を行っている。 1)BAECに対するLyso-PCの活性化の指標として、どの蛋白がリン酸化を受けるかについて検討を重ねてきたが、その一つとしてplatelet endothelial cell adhesion molecule-1(PECAM-1)がリン酸化を受けることを見い出した。現在、リン酸化されたPECAM-1の意義づけ、リン酸化の分子機構について検討を重ねている。(論文投稿中) また、Lyso-PCの細胞内シグナル伝達経路の解明を進めているが、BEACを用いた系で、JNK、ERKの二つのKinaseのリン酸化が起こることを見い出し、その上流、下流における情報伝達系の解析を急いでいる。(論文準備中) 2)Tリンパ球を用いた、HB-EGF遺伝子の発現調節の分子機構について検討を続けているが、Lyso-PCは、IL-2存在下で、HB-EGFmRNAの発現誘導を惹起すること、さらにHB-EGFmRNAの安定化に関与している知見を得た。(Cir.Res.1997年in press) 現在、HB-EGF遺伝子の5′側プロモーター領域を解析することにより、転写調節の分子機構の解明を急いでいる。また、Tリンパ球に、Lyso-PCを作用させると、IFN-γmRNAの発現誘導、さらにIFN-γmRNAの安定化にも関与していることを新たに見い出したので、その解析を合わせて行なっている。この様なアプローチから、Lyso-PCがいかなる機構で、細胞内に情報を伝えていくかを明らかにして行きたい。

研究成果

(20件)

すべてその他

すべて文献書誌 (20件)

[文献書誌] Tanaka,M.et al.: "Regulation of apolipoprotein B secretion in hepatocytes from Watanabe heritable hyperlipidemic rabbit,an animal model of familial hypercholesterolemia." Athrosclerosis. 114. 73-82 (1995)
[文献書誌] Ochi,H.et al: "Elevated levels of cyclic AMP inhibits protein kinase-C independent mechanisms of endothelialial PDGF-B chain and TCAM-1 gene induction by lysophosphatidylchline." Circulation Research. 77. 530-535 (1995)
[文献書誌] Kita,T.et al.: "Lessons concerning human lipoprotein metabolism from the study of the WHHL rabbit." Atherosclerosis. X. 111-113 (1995)
[文献書誌] Uematsu,M.et al.: "Coexistent myelodysplastic syndrome and non-Hodgkin lymphoma. Report of a case and review of the literature." Int.J.Hematology. 62. 45-51 (1995)
[文献書誌] Kume,N.et al.: "Involvement of protein kinase C-independent mechanisms in endothelial ICAM-1 up-regulation by lysophosphatidylcholine." Ann.N.Y.Acad.Sci.748. 541-542 (1995)
[文献書誌] Komatsu,T.et al.: "Lipoprotein glomerulopathy with a new apolipoprotein E phenotype" Am.J.Kidney Diseases. 25. 952-953 (1995)
[文献書誌] Nishida,R.et al.: "Endoscopic Sclerotherapy in a Rat Model of Esophageal Varices" Scand J.Gastroenterol. 30. 489-496 (1995)
[文献書誌] Dekigai,H.et al: "Mechanism of Helicobacter pylori-Associated Gastric Mucosal Injury" Digestive Diseases and Sceiences. 40. 1332-1339 (1995)
[文献書誌] Teramoto,T.et al.: "Clinical Efficacy of fluvastatin for hyperlipidemia in Japanese patients." Am.J.Cardiol.76. 33A-36A (1995)
[文献書誌] Yokode,M.et al.: "The macrophage and its role in atherogenesis" Internal Medicine. 34. 281-283 (1995)
[文献書誌] Yokode,M.et al.: "Cigarette smoke and lipoprotein modification : a possible interpretation for development of atherosclerosis." Ann.N.Y.Acad Sci.748. 294-301 (1995)
[文献書誌] Iehara,N,et al.: "Differentiation of smooth muscle phenotypes in mouse mesangial cells." Kid.Int.49. 133-134 (1996)
[文献書誌] Iehara,N,et al.: "Advanced glycosylation endoproducts modulate transcriptional regulations of type IV collagen and α-smooth muscle action on mesangial cells." Nephrology. 118. 141-146 (1996)
[文献書誌] Uematsu-Yanagita,M.et al.: "Microscopic polyarteritis during polymyalgia rheumatica remission." Am.J.Kid.Dis.28. 289-291 (1996)
[文献書誌] Yokode,M.et al.: "Modification of high-and low-denistylipoproteins by cigarette smoke oxidants." The Ann.N.Y.Acad.Sci. 786. 245-251 (1996)
[文献書誌] Kita,T.et al.: "Lysophosphatidylcholine induced gene expression of endothelial platelet-derived growth factor-b-chain and intercellular adbesion molecule-1" Medical Science Symposia Series. (in press).
[文献書誌] Kita,T.et al.: "Induction of endothelial platelet-derived growth factor-b-chain and intercellular adhesion molecule-1 by lysophosphatidylcholine" The Ann.N.Y.Acad.Sci.(in press).
[文献書誌] Sakai,A.et al.: "P-selection and vascular cell adhesion molecule-l are focally expressed in aortas of hypercholesterolemic rabbits prior to intimal accumulation of Macrophages and T-lymphocytes." Arterioscler Thromb Vasc Biol.(in press).
[文献書誌] Nishi,E.et al.: "Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T-lymphocytes." Circulation Research. (in press).
[文献書誌] Sawamura,T.et al: "Anovel endothelial receptor for oxidized LDL" Nature. (in press).

1996 年度 実績報告書

動脈硬化発症、進展の病態に関する分子生物学的研究

研究代表者

北 徹 京都大学, 医学研究科, 教授 (60161460)

研究成果

[文献書誌] Tanaka,M.et al.: "Regulation of apolipoprotein B secretion in hepatocytes from Watanabe heritable hyperlipidemic rabbit,an animal model of familial hypercholesterolemia." Athrosclerosis. 114. 73-82 (1995)

[文献書誌] Ochi,H.et al: "Elevated levels of cyclic AMP inhibits protein kinase-C independent mechanisms of endothelialial PDGF-B chain and TCAM-1 gene induction by lysophosphatidylchline." Circulation Research. 77. 530-535 (1995)

[文献書誌] Kita,T.et al.: "Lessons concerning human lipoprotein metabolism from the study of the WHHL rabbit." Atherosclerosis. X. 111-113 (1995)

[文献書誌] Uematsu,M.et al.: "Coexistent myelodysplastic syndrome and non-Hodgkin lymphoma. Report of a case and review of the literature." Int.J.Hematology. 62. 45-51 (1995)

[文献書誌] Kume,N.et al.: "Involvement of protein kinase C-independent mechanisms in endothelial ICAM-1 up-regulation by lysophosphatidylcholine." Ann.N.Y.Acad.Sci.748. 541-542 (1995)

[文献書誌] Komatsu,T.et al.: "Lipoprotein glomerulopathy with a new apolipoprotein E phenotype" Am.J.Kidney Diseases. 25. 952-953 (1995)

[文献書誌] Nishida,R.et al.: "Endoscopic Sclerotherapy in a Rat Model of Esophageal Varices" Scand J.Gastroenterol. 30. 489-496 (1995)

[文献書誌] Dekigai,H.et al: "Mechanism of Helicobacter pylori-Associated Gastric Mucosal Injury" Digestive Diseases and Sceiences. 40. 1332-1339 (1995)

[文献書誌] Teramoto,T.et al.: "Clinical Efficacy of fluvastatin for hyperlipidemia in Japanese patients." Am.J.Cardiol.76. 33A-36A (1995)

[文献書誌] Yokode,M.et al.: "The macrophage and its role in atherogenesis" Internal Medicine. 34. 281-283 (1995)

[文献書誌] Yokode,M.et al.: "Cigarette smoke and lipoprotein modification : a possible interpretation for development of atherosclerosis." Ann.N.Y.Acad Sci.748. 294-301 (1995)

[文献書誌] Iehara,N,et al.: "Differentiation of smooth muscle phenotypes in mouse mesangial cells." Kid.Int.49. 133-134 (1996)

[文献書誌] Iehara,N,et al.: "Advanced glycosylation endoproducts modulate transcriptional regulations of type IV collagen and α-smooth muscle action on mesangial cells." Nephrology. 118. 141-146 (1996)

[文献書誌] Uematsu-Yanagita,M.et al.: "Microscopic polyarteritis during polymyalgia rheumatica remission." Am.J.Kid.Dis.28. 289-291 (1996)

[文献書誌] Yokode,M.et al.: "Modification of high-and low-denistylipoproteins by cigarette smoke oxidants." The Ann.N.Y.Acad.Sci. 786. 245-251 (1996)

[文献書誌] Kita,T.et al.: "Lysophosphatidylcholine induced gene expression of endothelial platelet-derived growth factor-b-chain and intercellular adbesion molecule-1" Medical Science Symposia Series. (in press).

[文献書誌] Kita,T.et al.: "Induction of endothelial platelet-derived growth factor-b-chain and intercellular adhesion molecule-1 by lysophosphatidylcholine" The Ann.N.Y.Acad.Sci.(in press).

[文献書誌] Sakai,A.et al.: "P-selection and vascular cell adhesion molecule-l are focally expressed in aortas of hypercholesterolemic rabbits prior to intimal accumulation of Macrophages and T-lymphocytes." Arterioscler Thromb Vasc Biol.(in press).

[文献書誌] Nishi,E.et al.: "Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T-lymphocytes." Circulation Research. (in press).

[文献書誌] Sawamura,T.et al: "Anovel endothelial receptor for oxidized LDL" Nature. (in press).

1996 年度実績報告書

北徹京都大学, 医学研究科, 教授 (60161460)