1996 Fiscal Year Annual Research Report

動脈硬化発症、進展の病態に関する分子生物学的研究

Research Project

Project/Area Number	08407026
Research Category	Grant-in-Aid for Scientific Research (A)
Research Institution	Kyoto University
Principal Investigator	北徹京都大学, 医学研究科, 教授 (60161460)
Co-Investigator(Kenkyū-buntansha)	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)
Keywords	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
Research Abstract	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。

Research Products

(20 results)

All Other

All Publications (20 results)

[Publications] 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)
[Publications] 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)
[Publications] Kita,T.et al.: "Lessons concerning human lipoprotein metabolism from the study of the WHHL rabbit." Atherosclerosis. X. 111-113 (1995)
[Publications] 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)
[Publications] 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)
[Publications] Komatsu,T.et al.: "Lipoprotein glomerulopathy with a new apolipoprotein E phenotype" Am.J.Kidney Diseases. 25. 952-953 (1995)
[Publications] Nishida,R.et al.: "Endoscopic Sclerotherapy in a Rat Model of Esophageal Varices" Scand J.Gastroenterol. 30. 489-496 (1995)
[Publications] Dekigai,H.et al: "Mechanism of Helicobacter pylori-Associated Gastric Mucosal Injury" Digestive Diseases and Sceiences. 40. 1332-1339 (1995)
[Publications] Teramoto,T.et al.: "Clinical Efficacy of fluvastatin for hyperlipidemia in Japanese patients." Am.J.Cardiol.76. 33A-36A (1995)
[Publications] Yokode,M.et al.: "The macrophage and its role in atherogenesis" Internal Medicine. 34. 281-283 (1995)
[Publications] 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)
[Publications] Iehara,N,et al.: "Differentiation of smooth muscle phenotypes in mouse mesangial cells." Kid.Int.49. 133-134 (1996)
[Publications] 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)
[Publications] Uematsu-Yanagita,M.et al.: "Microscopic polyarteritis during polymyalgia rheumatica remission." Am.J.Kid.Dis.28. 289-291 (1996)
[Publications] Yokode,M.et al.: "Modification of high-and low-denistylipoproteins by cigarette smoke oxidants." The Ann.N.Y.Acad.Sci. 786. 245-251 (1996)
[Publications] 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).
[Publications] 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).
[Publications] 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).
[Publications] Nishi,E.et al.: "Lysophosphatidylcholine increases expression of heparin-binding epidermal growth factor-like growth factor in human T-lymphocytes." Circulation Research. (in press).
[Publications] Sawamura,T.et al: "Anovel endothelial receptor for oxidized LDL" Nature. (in press).

1996 Fiscal Year Annual Research Report

動脈硬化発症、進展の病態に関する分子生物学的研究

Principal Investigator

北 徹 京都大学, 医学研究科, 教授 (60161460)

Research Products

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

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

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

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

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

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

[Publications] 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)

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

[Publications] 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)

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

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

[Publications] 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).

[Publications] 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).

[Publications] 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).

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

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

北徹京都大学, 医学研究科, 教授 (60161460)