1992 年度実績報告書

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

研究課題

研究課題/領域番号	04304051
研究機関	京都大学
研究代表者	北徹京都大学, 医学部, 教授 (60161460)
研究分担者	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)
キーワード	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
研究概要	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。

研究成果
(21件)

すべてその他

すべて文献書誌 (21件)

[文献書誌] 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.
[文献書誌] 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.
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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)
[文献書誌] 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 年度 実績報告書

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

研究代表者

北 徹 京都大学, 医学部, 教授 (60161460)

研究成果

[文献書誌] 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.

[文献書誌] 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.

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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)

[文献書誌] 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 年度実績報告書

北徹京都大学, 医学部, 教授 (60161460)