Activation of human matrix metalloproteinases by various bacterial proteinases
Activation of human matrix metalloproteinases by various bacterial proteinases
复制标题
DOI：
10.1074/jbc.272.9.6059
复制
发表时间：
1997-02-28
影响因子：
4.8
通讯作者：
Maeda, H
中科院分区：
文献类型：
--
作者：
Okamoto, T;Akaike, T;Maeda, H
基质金属蛋白酶（MMPs）是一类含锌蛋白酶，在生理和病理条件下参与组织重塑。为了测试细菌蛋白酶在细菌感染期间组织损伤中的参与，我们研究了各种细菌蛋白酶对从人嗜中性粒细胞（proMMP-8和-9）和从人纤维肉瘤细胞（proMMP-1）纯化的MMP前体（proMMP）的活化潜力。用一系列摩尔比为0.01-0.1（细菌蛋白酶与proMMP）的细菌蛋白酶处理每种proMMP，并测定产生的MMP的活性。在六种不同的细菌蛋白酶中，嗜热菌蛋白酶家族酶（M4家族）如铜绿假单胞菌弹性蛋白酶、霍乱弧菌蛋白酶和嗜热菌蛋白酶通过有限的蛋白水解强烈激活所有三种proMMP以产生MMP的活性形式，活性MMP的N-末端序列分析揭示了在proMMP-1和proMMP-9的瓦尔（82）-Leu（83）和Thr（90）-Phe（91）键处发生切割，它们分别位于MMP催化结构域的N末端附近。相比之下，沙雷氏菌属56-kDa蛋白酶和假单胞菌属碱性蛋白酶（两者都被归类为锌金属蛋白酶的serralysin亚家族（家族M10）的成员）和沙雷氏菌属73-kDa巯基蛋白酶在这些实验条件下没有证据表明proMMP-1、-8和-9的蛋白水解加工或活化。这些结果表明，细菌蛋白酶可能在感染部位的组织破坏和细胞外基质分解中起重要作用。
Matrix metalloproteinases (MMPs) are zinc-containing proteinases that participate in tissue remodeling under physiological and pathological conditions. To test the involvement of bacterial proteinases in tissue injury during bacterial infections, we investigated the activation potential of various bacterial proteinases against precursors of MMPs (proMMPs) purified from human neutrophils (proMMP-8 and -9) and from human fibrosarcoma cells (proMMP-1). Each proMMP was subjected to treatment with a series of bacterial proteinases at molar ratios of 0.01-0.1 (bacterial proteinase to proMMP), and activities of MMPs generated were determined. Among six different bacterial proteinases, thermolysin family enzymes (family M4) such as Pseudomonas aeruginosa elastase, Vibrio cholerae proteinase, and thermolysin strongly activated all three proMMPs via limited proteolysis to generate active forms of the MMPs, N-terminal sequence analysis of the active MMPs revealed that cleavage occurred at the Val(82)-Leu(83) and Thr(90)-Phe(91) bonds of proMMP-1 and proMMP-9, respectively, which are located near the N terminus of the catalytic domain of MMPs. In contrast, Serratia 56-kDa proteinase and Pseudomonas alkaline proteinase, both of which are classified as members of the serralysin subfamily of zinc metalloproteinases (family M10), and Serratia 73-kDa thiol proteinase did mot evidence proteolytic processing or activation of proMMP-1, -8, and -9 under these experimental conditions. These results indicate that bacterial proteinases may play an important role in tissue destruction and disintegration of extracellular matrix at the site of infections.