Inhibition of a snake venom hemorrhagic metalloproteinase by human and rat α-macroglobulins

被引：22

作者：

Anai, K ^{[1
]}

Sugiki, M ^{[1
]}

Yoshida, E ^{[1
]}

Maruyama, M ^{[1
]}

机构：

[1] Miyazaki Med Coll, Dept Physiol, Kiyotake, Miyazaki 88916, Japan

来源：

TOXICON | 1998年 / 36卷 / 08期

关键词：

D O I：

10.1016/S0041-0101(98)00081-6

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Jararafibrase I is a hemorrhagic metalloproteinase purified from Bothrops jararaca venom, which induces local hemorrhage by degrading the basement membrane components. The present study was undertaken to investigate the inhibition of jararafibrase I by human and rat serum proteinase inhibitors. The proteolytic activity of jararafibrase I was completely inhibited by human and rat sera. In particular, rat serum displayed a greater inhibitory capacity. The inhibitory capacities of both sera were dependent on alpha-macroglobulins. SDS-PAGE analysis revealed that jararafibrase I formed complexes with alpha-macroglobulins that were present in normal sera. The proteolytic activity of jararafibrase I was completely inhibited by alpha 1-macroglobulin and murinoglobulin in rat serum, and by human alpha 2-macroglobulin. The inhibition molar ratios of alpha-macroglobulin/jararafibrase I were 1.5 for rat alpha 1-macroglobulin and human alpha 2-macroglobulin, and 2.4 for rat murinoglobulin. SDS-PAGE under reducing conditions demonstrated that the bait region of human alpha 2-macroglobulin and rat murinoglobulin was cleaved by jararafibrase I. The bait region cleavage sites were identified as being situated at the (696)Arg-(697)Leu peptide bond in human alpha 2-macroglobulin, and at the (686)Ala-(687)Val peptide bond in rat murinoglobulin. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：1127 / 1139

页数：13

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