1992 Fiscal Year Annual Research Report

動脈硬化症の分子生物学的解析と予防・抑制対策に関する総合的研究

Research Project

Project/Area Number	04304051
Research Institution	Kyoto University
Principal Investigator	北徹京都大学, 医学部, 教授 (60161460)
Co-Investigator(Kenkyū-buntansha)	堀内正公熊本大学, 医学部, 教授 (10117377) 山田信博東京大学, 医学部, 助手 (40200729) 齋藤康千葉大学, 医学部, 講師 (50101358) 松沢佑次大阪大学, 医学部, 教授 (70116101) 高井義美神戸大学, 医学部, 教授 (60093514)
Keywords	リゾフォスファチジルコリン / 酸化LDL / HDL / マクロファージ / CETP / 増殖因子 / M-CSF / Small G Protein
Research Abstract	1)血管内皮細胞障害、あるいは活性化動脈硬化惹起物質として重要な役割を果たす酸化LDLの成分のうち、リゾフォスファチジルコリン(LSO-PC)がヒト臍帯内皮細胞の単球接着分子ICAM-1の発現及び単球走化因子MCP-1の発現誘導を起こすことを見い出した。 2)マクロファージ(MΦ)の泡沫化、脱泡沫化酸化LDLがそれに特異的なMΦの受容体を介して泡沫化を起こすことが明らかになった。HDLは脱泡沫化に関与しているが、酸化を起こすことにより、脱泡沫化が抑制されることがわかり、この結果HDL構造蛋白A-1が重要であることがわかった。脱泡沫化にCETPの関与を含めて検討中である。 3)平滑筋細胞(SMC)増殖制御 SMC走化因子の単離に成功し、クローニング中である。またSMCへのPDGFの影響をMCSF、c-fms遺伝子の発現を指標に検討中である。またSMCの機能に与えるsmall G蛋白の関与についても検討中である。この様に血管壁細胞の動脈硬化発生からみた細胞生物学的、分子生物学的検討を進めている。

Research Products
(21 results)

All Other

All Publications (21 results)

[Publications] Tanaka,M.,Jingami,H.,Otani,H.,Cho,M.,Ueda,Y.,Arai,H.,Nagano,Y.,Doi,T.& Kita,T.: "Regulation of apolipoprotein B production and secretion in response to the change of intracellular cholestery ester contents in rabbit hepatocytes." J.Biol.Chem.
[Publications] Ueda,Y.,Arai,H.,Kawashima,A.,Nagano,Y.Cho,M.,Tanaka,M.& Kita,T.: "Different expression of modified low density lipoprotein receptors in rabbit peritoneal macrophages and kupffer cells." Atherosclerosis.
[Publications] Hara,S.,Nagano,Y.,Sasada,M.& Kita,T.: "Probucol pre-treatment enhances the chemotaxis of mouse peritoneal macrophages." Arteriosclerosis and Thrombosis. 12. 593-600 (1992)
[Publications] Hirata,K.,Kikuch,A.,sasaki,T.,Kuroda,S.,Kaibuchi,K.,Matsuura,Y.,Seki,H.,Saida,K.& Takai,Y.: "Involvement of rho p21 in the GTP-enhanced calcium ion sensitivity of smooth muscle contraction." J.Biol.Chem.267. 8719-8722 (1992)
[Publications] Kikuchi,A.,Kuroda,S.,Sasaki,T.,Kotani,K.,Hirata,K.,Katayama,M.& Takai,Y.: "Functional interactions of stimulatory and inhibitory GDP/GTP exchange proteins and their common substrate small GTP-binding protein." J.Biol.Chem.267. 14611-14615 (1992)
[Publications] Yoshida,Y.,Kawata,M.,Miura,Y.,Musha,T.,Sasaki,T.,Kikuchi,A.& Takai,Y.: "Microinjection of smg/rap1Krev-1 p21 into Swiss 3T3 cells induces DNA synthesis and morphological changes." Molecular and Cellular Biology. 12. 3407-3414 (1992)
[Publications] Nozaki,S.,Shimomura,I.,Funahashi,T.,Menju,M.,Kubo,M.& Matsuzawa,Y.: "Stimulation of the activity and mRNA level of hepatic triacylglycerol lipase by triiodothyronine in HepG2 cells." Biochim.Biophys.Acta. 1127. 298-302 (1992)
[Publications] Nakamura,T.,Ueyama,Y.,Funahashi,T.,Yamashita,S.,Kameda Takemura,K.,Kubo,M.,Yamada,K.& Matsuzawa,Y.: "Non-macrophage-related accumulation of cholesterol during probucol treatment in familial hypercholestrolemia:report of two." Atherosclerosis. 92. 193-202 (1992)
[Publications] Shimomura,I.,Tokunaga,K.,Jiao,S.,Funahashi,T.,Keno,Y.,Kobatake,T.,Kotani,K.,Suzuki,H.,Yamamoto,T.,Tarui.S.& Matsuzawa.Y.: "Marked enhancement of acy-CoA synthe tase activity and mRNA,paralleled to lipoprotein lipase mRNA,in adipose tissues of Zucker obese rats(fa/fa)." Biochim.Biophys.Acta. 1124. 112-118 (1992)
[Publications] Morisaki,N.,Koyama,N.,Kawano,M.,Mori,S.,Umemiya,K.,Koshikawa,T.,Saito,Y.& Yoshida,S.: "Human macrophages modulate the phenotype of cultured rabit aortic smooth muscle cells through secretion of platelet-derived growth factor." European Journal of Clinical In vestigation. 22. 461-468 (1992)
[Publications] Koyama,N.,Morisaki,N.,Saito,Y.& Yoshida,S.: "Regulatory efects of platelet-derived growth factor-AA homodimer on migration of vascular smooth muscle cells." J.Biol.Chem.267. 22806-22812 (1992)
[Publications] Shinomiya,M.,Shirai,K.,Saito,Y.& Yoshida,S.: "Inhibition of intimal thickening of the carotid artery of rabbits and of outgrowth of explants of aorta by probucol." Atherosclerosis. 97. 143-148 (1992)
[Publications] Inaba,T.,Yamada,N.,Gotoda,T.,Shimano,H.,Shimada,M.,Kadowaki,T.,Momomura,K.,Motoyoshi,K.,Tsukada,T.,Morisaki,N.,Saito,Y.,Yoshida,S.,Takaku,F.& Yazaki,Y.: "Expression of M-CSF receptor encoded by c-fms on smooth muscle cells derived from arteriosclerotic lesion." J.Biol.Chem.267. 5693-5699 (1992)
[Publications] Inaba,T.,Gotoda,T.,Shimano,H.,Shimada,M.,Harada,K.,Kozaki,K.,Watanabe,Y.,Ho,E.,Motoyoshi,K.,Yazaki,Y.& Yamada,N.: "PDGF induces cfms and scavenger receptor genes in vascular smooth muscle cells." J.Biol.Chem.267. 13107-13112 (1992)
[Publications] Shimada,M.,Yamada,N.,Inaba,T.,Shimano,H.,Gotoda,T.,WAtanabe,Y.,Yamamoto,K.,Motoyoshi,K.Yazaki,Y.: "Platelet-derived growth factor BB-dimer suppresses the expression of macrophage colony-stimulating factor in human vascular smooth muscle cells." J.Biol.Chem.267. 15455-15458 (1992)
[Publications] Shinohara,M.,Miyazaki,A.,Shichir,M.,Morino,Y.& Horiuchi,S.: "Exposure of rat peritoneal macropahges to acetylated low Density lipoprotein results in release of plasma membrane cholesterol;an efficen substrate for esteriffication by acyl CoA:cholesterole acyl transferase." J.Biol.Chem.267. 1603-1608 (1992)
[Publications] Araki,N.,Ueno,N.,Chakrabarti,B.,Morino,Y.& Horiuchi,S.: "Immunochemical evidence for the presence of advanced glycation end products in human lens proteins and its positive correlation with aging." J.Biol.Chem.267. 10211-10214 (1992)
[Publications] Sakai,M.,Miyazaki,A.,Sakamoto,Y.,Shichir M.& Horiuchi,S.: "Cross-linking of apolipoproteins is involved in a loss of the ligand activity of high density lipoprotein upon Cu<@D12+@>D1-mediated oxidation." FEBS Letts.314. 199-202 (1992)
[Publications] Shimomura,I.,tokunaga,K.,Jiao,S.,Funahashi,T.,Keno,Y.,Kobatake,T.,Kotani,K.,Suzuki,H.,Yamamoto,T.,Tarui,S.& Matsuzawa,Y.: "Marked enhancement of acyl-CoA synthetase activity and mRNA,paralleled to lipoprotein lipase mRNA,in adipose tissues of Zucker obese rats(fa/fa)." Biochim.Biophys.Acta.1124. 112-118 (1992)
[Publications] Kumabe,T.,Sohma,Y.,Kayama,T.,Yoshimoto,T.& Yamamoto,T.: "Ampliffication of a-platelet-derived growth factor receptor gene lacking an exon coding for a portion of the extracellular region in a primary brain tumor of glial origin." Oncogene. 7. 627-633 (1992)
[Publications] Takahashi,S.,Kawarabayasi,Y.,Nakai,T.,Sakai,J.& Yamamoto,T.: "Rabbit very low density lipoprotein receptor:A low density lipoprotein receptor-like protein with distinct ligand specifficity." Proc.Natl.Acad.Sci.USA. 89. 9252-9256 (1992)

1992 Fiscal Year Annual Research Report

動脈硬化症の分子生物学的解析と予防・抑制対策に関する総合的研究

Principal Investigator

北 徹 京都大学, 医学部, 教授 (60161460)

Research Products

[Publications] Tanaka,M.,Jingami,H.,Otani,H.,Cho,M.,Ueda,Y.,Arai,H.,Nagano,Y.,Doi,T.& Kita,T.: "Regulation of apolipoprotein B production and secretion in response to the change of intracellular cholestery ester contents in rabbit hepatocytes." J.Biol.Chem.

[Publications] Ueda,Y.,Arai,H.,Kawashima,A.,Nagano,Y.Cho,M.,Tanaka,M.& Kita,T.: "Different expression of modified low density lipoprotein receptors in rabbit peritoneal macrophages and kupffer cells." Atherosclerosis.

[Publications] Hara,S.,Nagano,Y.,Sasada,M.& Kita,T.: "Probucol pre-treatment enhances the chemotaxis of mouse peritoneal macrophages." Arteriosclerosis and Thrombosis. 12. 593-600 (1992)

[Publications] Hirata,K.,Kikuch,A.,sasaki,T.,Kuroda,S.,Kaibuchi,K.,Matsuura,Y.,Seki,H.,Saida,K.& Takai,Y.: "Involvement of rho p21 in the GTP-enhanced calcium ion sensitivity of smooth muscle contraction." J.Biol.Chem.267. 8719-8722 (1992)

[Publications] Kikuchi,A.,Kuroda,S.,Sasaki,T.,Kotani,K.,Hirata,K.,Katayama,M.& Takai,Y.: "Functional interactions of stimulatory and inhibitory GDP/GTP exchange proteins and their common substrate small GTP-binding protein." J.Biol.Chem.267. 14611-14615 (1992)

[Publications] Yoshida,Y.,Kawata,M.,Miura,Y.,Musha,T.,Sasaki,T.,Kikuchi,A.& Takai,Y.: "Microinjection of smg/rap1Krev-1 p21 into Swiss 3T3 cells induces DNA synthesis and morphological changes." Molecular and Cellular Biology. 12. 3407-3414 (1992)

[Publications] Nozaki,S.,Shimomura,I.,Funahashi,T.,Menju,M.,Kubo,M.& Matsuzawa,Y.: "Stimulation of the activity and mRNA level of hepatic triacylglycerol lipase by triiodothyronine in HepG2 cells." Biochim.Biophys.Acta. 1127. 298-302 (1992)

[Publications] Nakamura,T.,Ueyama,Y.,Funahashi,T.,Yamashita,S.,Kameda Takemura,K.,Kubo,M.,Yamada,K.& Matsuzawa,Y.: "Non-macrophage-related accumulation of cholesterol during probucol treatment in familial hypercholestrolemia:report of two." Atherosclerosis. 92. 193-202 (1992)

[Publications] Koyama,N.,Morisaki,N.,Saito,Y.& Yoshida,S.: "Regulatory efects of platelet-derived growth factor-AA homodimer on migration of vascular smooth muscle cells." J.Biol.Chem.267. 22806-22812 (1992)

[Publications] Shinomiya,M.,Shirai,K.,Saito,Y.& Yoshida,S.: "Inhibition of intimal thickening of the carotid artery of rabbits and of outgrowth of explants of aorta by probucol." Atherosclerosis. 97. 143-148 (1992)

[Publications] Inaba,T.,Gotoda,T.,Shimano,H.,Shimada,M.,Harada,K.,Kozaki,K.,Watanabe,Y.,Ho,E.,Motoyoshi,K.,Yazaki,Y.& Yamada,N.: "PDGF induces cfms and scavenger receptor genes in vascular smooth muscle cells." J.Biol.Chem.267. 13107-13112 (1992)

[Publications] Shimada,M.,Yamada,N.,Inaba,T.,Shimano,H.,Gotoda,T.,WAtanabe,Y.,Yamamoto,K.,Motoyoshi,K.Yazaki,Y.: "Platelet-derived growth factor BB-dimer suppresses the expression of macrophage colony-stimulating factor in human vascular smooth muscle cells." J.Biol.Chem.267. 15455-15458 (1992)

[Publications] Araki,N.,Ueno,N.,Chakrabarti,B.,Morino,Y.& Horiuchi,S.: "Immunochemical evidence for the presence of advanced glycation end products in human lens proteins and its positive correlation with aging." J.Biol.Chem.267. 10211-10214 (1992)

[Publications] Sakai,M.,Miyazaki,A.,Sakamoto,Y.,Shichir M.& Horiuchi,S.: "Cross-linking of apolipoproteins is involved in a loss of the ligand activity of high density lipoprotein upon Cu<@D12+@>D1-mediated oxidation." FEBS Letts.314. 199-202 (1992)

[Publications] Kumabe,T.,Sohma,Y.,Kayama,T.,Yoshimoto,T.& Yamamoto,T.: "Ampliffication of a-platelet-derived growth factor receptor gene lacking an exon coding for a portion of the extracellular region in a primary brain tumor of glial origin." Oncogene. 7. 627-633 (1992)

[Publications] Takahashi,S.,Kawarabayasi,Y.,Nakai,T.,Sakai,J.& Yamamoto,T.: "Rabbit very low density lipoprotein receptor:A low density lipoprotein receptor-like protein with distinct ligand specifficity." Proc.Natl.Acad.Sci.USA. 89. 9252-9256 (1992)

北徹京都大学, 医学部, 教授 (60161460)