Engineering Autoactivating Forms of Matrix Metalloproteinase-9 and Expression of the Active Enzyme in Cultured Cells and Transgenic Mouse Brain

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• 作者：Katherine E. Fisher ; Qing Fei ; Ellen R. Laird ; Jeffrey L. Stock ; Melanie R. Allen ; Barbara G. Sahagan ; and Christine A. Strick
• 刊名：Biochemistry
• 出版年：2002
• 出版时间：July 2, 2002
• 年：2002
• 卷：41
• 期：26
• 页码：8289 - 8297
• 全文大小：514K
• 年卷期：v.41,no.26(July 2, 2002)
• ISSN：1520-4995

文摘

Matrix metalloproteinases (MMPs) are hypothesized to play an important role in thepathogenesis of several central nervous system disorders. Increased levels of expression of MMP-9(gelatinase B) and MMP-2 (gelatinase A) have been observed in Alzheimer's disease, stroke, multiplesclerosis, and amyotrophic lateral sclerosis. This suggests an aberrant regulation of MMPs that could leadto inappropriate expression of MMP activity. To allow us to evaluate the effect of increased levels ofactive MMP-9 in the central nervous system, mutant forms of the enzyme were designed to autocatalyticallyremove the pro domain, yielding active enzyme. This was accomplished by modifying residues in thecysteine switch autoinhibitor region of the propeptide. Stable cell lines and transgenic mice that expressG100L and D103N autoactive forms of human MMP-9 were developed to study the role of dysregulationof MMP-9 in disease.