Activation and novel processing of matrix metalloproteinases by a thiol proteinase from the oral anaerobe Porphyromonas gingivalis
Activation and novel processing of matrix metalloproteinases by a thiol proteinase from the oral anaerobe Porphyromonas gingivalis
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DOI：
10.1177/00220345970760060501
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发表时间：
1997-06-01
影响因子：
7.6
通讯作者：
BirkedalHansen, H
中科院分区：
文献类型：
--
作者：
DeCarlo, AA;Windsor, LJ;BirkedalHansen, H
牙周疾病的一个关键后果是连接牙弓中牙齿与骨骼的胶原性牙周韧带的降解。牙周疾病是由牙齿上的细菌定植引发的，但它们的分子发病机制仍然是推测性的。一类被称为基质金属蛋白酶（MMPs）的酶与牙周韧带的降解有关。MMPs也被怀疑在许多其他生理和病理重塑过程中起作用，它可由牙齿周围的上皮细胞分泌，并且在牙周病患病部位附近的组织和体液中大量存在。由于大多数MMPs是以无活性的酶原形式分泌的，可能通过有限的蛋白水解作用被激活，所以有人提出，感染牙周病原体所表达的蛋白酶可能激活潜在的宿主MMPs，从而引发或加速胶原性牙周韧带的降解。这项工作的目的是研究纯化的宿主MMPs与细菌蛋白酶之间的相互作用。在本文中，我们证明从牙周病原体牙龈卟啉单胞菌中分离出的一种蛋白酶能够激活MMP - 1、MMP - 3和MMP - 9，并能催化由MMP - 3对MMP - 1的超激活。这些MMPs的激活被证明是由其前肽内的初始水解导致的。此外，对于MMP - 1和MMP - 9，牙龈卟啉单胞菌蛋白酶在一个先前未报道的位点的赖氨酸残基之后切割MMP前肽，对于这两种MMPs，该位点是已知自催化切割位点的氨基末端的一个残基。这些数据描述了牙周病原体牙龈卟啉单胞菌的一种致病模式，涉及宿主降解酶的激活。
A critical outcome of periodontal disease is degradation of the collagenous periodontal ligament that connects teeth to bone in the dental arch. Periodontal diseases occur in response to bacterial colonization of the teeth, but their molecular pathogenesis is still speculative. One family of enzymes, known as the matrix metalloproteinases (MMPs), has been implicated in the degradation of the periodontal ligament. MMPs, which are also suspected to play a role in many other physiologic and pathologic remodeling processes, can be secreted by epithelial cells surrounding the teeth and are found in relative abundance in tissues and fluids near periodontally diseased sites. Since most MMPs are secreted as inactive zymogens which may be activated by limited proteolysis, it has been suggested that proteinases expressed by the infecting periodontal pathogens might activate latent host MMPs to initiate or accelerate degradation of the collagenous periodontal ligament. The aim of this work was to examine interactions between purified host MMPs and bacterial proteinase. Ln this article, we demonstrate that a proteinase isolated from the periodontopathogen Porphyromonas gingivalis can activate MMP-1, MMP-3, and MMP-9 and can catalyze the superactivation of MMP-1 by MMP-3. Activation of these Mh?Ps is demonstrated to result from initital hydrolysis within their propeptide. Also, for MMP-1 and MMP-9: the P. gingivalis proteinase cleaves the MMP propeptide following a lysine residue at a previously unreported site which, for both MMPs, is one residue NH2-terminal to the known autocatalytic cleavage site. These data describe a mode of virulence for the periodontopathogen Porphyromonas gingivalis that involves activation of host-degradative enzymes.