Human Chymase, an Enzyme Forming Novel Bioactive 31-Amino Acid Length Endothelins
Human Chymase, an Enzyme Forming Novel Bioactive 31-Amino Acid Length Endothelins
复制标题
人食糜酶，一种形成新型生物活性 31 个氨基酸长度内皮素的酶
作者：
Hiroshi Kido;Ayako Nakano;N. Okishima;H. Wakabayashi;F. Kishi;Yuta Nakaya;M. Yoshizumi;T. Tamaki
我们报道了人类凝乳酶在产生具有生物活性的31个氨基酸长度的内皮素(ETS)中的新作用，这可能在过敏和血管疾病中发挥作用。哮喘患者的支气管、动脉粥样硬化的血管组织和心肌肥厚的心肌组织中，ET样免疫反应和肥大细胞的积聚均显著增加。人肥大细胞的糜酶选择性地裂解大ET-1、-2和-3的Tyr31-Gly32键，产生新的具有生物活性的31个氨基酸长度的ETS(1-31)，而不产生任何进一步的降解产物。然而，来自其他物种的凝乳酶，人组织蛋白酶G和猪的α-糜蛋白酶，可以降解大的ETS。在10(-9)~10(-7)M浓度范围内，ETS(1-31)对大鼠气管和猪冠状动脉有不同程度的收缩作用，且呈剂量依赖关系。此外，ET-1(1-31)在10(-14)~10(-10)M浓度范围内可引起细胞内游离钙离子浓度显著升高。ETS(1-31)的收缩活性可能不是由磷酰胺敏感的ET转换酶(S)或其他糜蛋白酶和金属内肽酶转化为相应的ETS(1-21)的结果，因为在加入ET-1(1-31)之前用这些酶的抑制剂处理并不能显著抑制ETS(1-31)的收缩活性。
We report the novel role of human chymase in the production of bioactive 31-amino acid length endothelins (ETs), which may play a role in allergies and vascular diseases. In the bronchi of asthmatic patients, the vascular tissue in atherosclerosis, and the heart muscle in cardiac hypertrophy, both ET-like immunoreactivity and the accumulation of mast cells significantly increase. Chymase from human mast cells selectively cleaves big ET-1, -2 and -3 at their Tyr31-Gly32 bonds, and produces novel bioactive 31-amino acid length ETs, ETs(1-31), without any further degradation products. However, chymases from other species, human cathepsin G, and porcine alpha-chymotrypsin, degrade big ETs. ETs(1-31) at concentrations between 10(-9) M and 10(-7) M exhibited various contractile potencies in rat tracheae and porcine coronary arteries in a dose-dependent manner. Furthermore, ET-1(1-31) at concentrations between 10(-14) M and 10(-10) M caused a significant increase in the intracellular free Ca2+ concentration. The contractile activity of ETs(1-31) may not be the consequence of conversion to the corresponding ETs(1-21) by phosphoramidon-sensitive ET converting enzyme(s) or other chymotrypsin-type proteases and metallo-endopeptidases, because the contractile activity was not significantly inhibited on treatment with inhibitors of these proteases prior to the addition of ET-1(1-31).
从大鼠肥大细胞分离的分泌颗粒中胰凝乳蛋白酶样蛋白酶的底物特异性。
DOI：
10.1073/pnas.84.2.364
发表时间：
1987
影响因子：
11.1
作者：
LeTrong,H;Neurath,H;Woodbury,RG
通讯作者：
Woodbury,RG
中性粒细胞和肥大细胞蛋白酶将血管紧张素 I 快速转化为血管紧张素 II。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Reilly,CF;Tewksbury,DA;Schechter,NM;Travis,J
通讯作者：
Travis,J
四种小鼠肥大细胞食糜酶的三维模型。
DOI：
--
发表时间：
1993
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Sali,A;Matsumoto,R;McNeil,HP;Karplus,M;Stevens,RL
通讯作者：
Stevens,RL