A novel vasoactive peptide, 31-amino acid length endothelin, by human chymase and its relation to atherosclerosis

人食糜酶产生的一种新型血管活性肽，31 个氨基酸长度的内皮素及其与动脉粥样硬化的关系

• 批准号: 11670685
• 负责人: NAKAYA Yutaka
• 金额: $ 1.98万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670685/
• 关键词: endothelin; chymase; vascular smooth muscle; ETA receptor; ETB receptor; endothelium; nitric oxide; 動脈硬化; アンギオテンシン; 血管内皮細胞; 肥満細胞; エンドセリン合成酵素

Human chymase produces a novel endothelin-1 with 31 amino-acid length ET-1 (1-31), which is longer than conventional ET-1, ET-1 (1-21). The aim of our study was to investigate the role of ET-1 (1-31) on porcine coronary vascular smooth muscle cell (VSMC). BQ485, an ETA receptor antagonist, completely abolished ET-1 (1-31)-induced contraction, but BQ788, an ETB receptor antagonist, slightly enhanced it, suggesting that ET-1 (1-31) relaxes artery via endothelium. On endothelial cells, ET-1 (1-21) and ET-1 (1-31) increased [Ca2+]i and produced NO, both of which were significantly inhibited by BQ788 and not by BQ485. These results indicate that ET-1 (1-31) increased [Ca2+]i and produced NO in endothelial cells through ETB receptor similarly with ET-1 (1-21). Although the increase in [Ca(2+)](i) by ET-1 (1-31) and contraction of artery was 10 times weaker than that of ET-1 (1-21), ET-1 (1-31) showed equivalent potency in VSMC proliferation, c-fos/c-myc mRNA expression and cell cycle analysis with ET-1 (1-21). ET-1 (1-31) significantly induced expression of cyclin D1 but not those of cyclin D2 or D3. These effects were specifically inhibited by BQ485. These results indicate that ET-1 (1-31) also can involve a VSMC proliferation process such as atherosclerosis.

人糖化酶产生的新型内皮素-1具有31个氨基酸长度ET-1(1-31)，比传统的ET-1、ET-1（1-21）长。本研究旨在探讨ET-1（1-31）在猪冠状动脉血管平滑肌细胞（VSMC）中的作用。ETA受体拮抗剂BQ485完全消除ET-1（1-31）诱导的收缩，而ETB受体拮抗剂BQ788则略微增强其收缩，提示ET-1（1-31）通过内皮使动脉松弛。在内皮细胞上，ET-1（1-21）和ET-1（1-31）增加[Ca2+]i并产生NO， BQ788显著抑制了这两种作用，而BQ485则没有。这些结果表明，ET-1（1-31）与ET-1（1-21）类似，通过ETB受体增加内皮细胞中的[Ca2+]i并产生NO。虽然ET-1（1-31）对[Ca(2+)](i)的增加和动脉收缩的作用比ET-1（1-21）弱10倍，但ET-1（1-31）对VSMC增殖、c-fos/c-myc mRNA表达和细胞周期分析的作用与ET-1（1-21）相当。ET-1（1-31）显著诱导细胞周期蛋白D1的表达，而对细胞周期蛋白D2和D3的表达无显著影响。这些作用被BQ485特异性抑制。这些结果表明ET-1（1-31）也可以参与VSMC的增殖过程，如动脉粥样硬化。

项目成果

Nagata N,Niwa Y,Nakaya Y:: "A novel 31-amino-acid-length endothelin, ET-1 (1-31), can act as a biologically active peptide for vascular smooth muscle cells"Biochem Biophys Res Commun. 275. 595-600 (2000)

Nagata N、Niwa Y、Nakaya Y：“一种新型的 31 个氨基酸长度的内皮素，ET-1 (1-31)，可以作为血管平滑肌细胞的生物活性肽”Biochem Biophys Res Commun。

Takeji T,Nakaya Y,Kamada M,Maeda K,Saijo Y,Mitani R,Irahara M,Aono T: "Effect of a novel vasoconstrictor endothelin-1 (1-31) on human umbilical artery"Biochem Biophys Res Commun. 270. 622-624 (2000)

Takeji T、Nakaya Y、Kamada M、Maeda K、Saijo Y、Mitani R、Irahara M、Aono T：“新型血管收缩剂内皮素-1 (1-31) 对人脐动脉的影响”Biochem Biophys Res Commun。

Z.Li, Y.Niwa, K.Rokutan, and Y.Nakaya.: "Expression of endothelin-1 in macrophages and mast cells in hyperplastic human tonsils."FEBS Lett.. 457(3). 381-384 (1999)

Z.Li、Y.Niwa、K.Rokutan 和 Y.Nakaya.：“增生性人扁桃体巨噬细胞和肥大细胞中内皮素-1 的表达”。FEBS Lett.. 457(3)。

Y.Niwa, N.Nagata, M.Oka, T.Toyoshima, H.Akiyoshi, T.Wada, and Y.Nakaya.: "Production of nitric oxide from endothelial cells by 31-amino-acid- length endothelin-1, a novel vasoconstrictive product by human chymase"Life Sci.. 67(9). 1103-1109 (2000)

Y.Niwa、N.Nagata、M.Oka、T.Toyoshima、H.Akiyoshi、T.Wada 和 Y.Nakaya.：“通过 31 个氨基酸长度的内皮素-1 从内皮细胞产生一氧化氮，

Nagata N,Niwa Y,Nakaya Y: "A novel 31-amino-acid-length endothelin, ET-1(1-31) , can act as a biologically active peptide for vascular smooth muscle cells"Biochem Biophys Res Commun. 275. 595-600 (2000)

Nagata N、Niwa Y、Nakaya Y：“一种新型的 31 个氨基酸长度的内皮素，ET-1(1-31)，可以作为血管平滑肌细胞的生物活性肽”Biochem Biophys Res Commun。