Advances in assays of matrix metalloproteinases (MMPs) and their inhibitors

Cheng, Xian-Chao; Fang, Hao; Xu, Wenfang

doi:10.1080/14756360701511292

Cited by 29 publications

(23 citation statements)

References 109 publications

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“…Examining MMP activity is significant in the diagnosis and therapy of diseases associated with MMPs -i.e., illnesses of the salivary glands and skin [34].…”

Section: Methodsmentioning

confidence: 99%

The Significance of Matrix Metalloproteinases in Oral Diseases

et al. 2015

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MMPs are significant in the physiological processes of embryo development, wound healing and differentiation related to tissue remodeling. However, the overexpression of several MMPs is involved in tumor invasion, metastasis, disregulated angiogenesis, inflammation and even cell destruction [1,[5][6][7][8][9]. MMP SubfamiliesThe first metalloproteinase was discovered in 1962 during a study of the ECM degradation re- The Role of MMPsMatrix metalloproteinases (MMPs) belong to a family of structurally related zinc-dependent proteolytic enzymes that are known known to play a key role in the catabolic turnover of extracellular matrix (ECM) components. Research studies to date have indicated that MMPs regulate the activity of several non-ECM bioactive substrates, including growth factors, cytokines, chemokines and cell receptors, which determine the tissue microenvironment. These activities are implicated in a number of essential physiopathological processes AbstractMatrix metalloproteinases (MMPs) belong to a family of structurally related zinc-dependent proteolytic enzymes that are known to play a key role in the catabolic turnover of extracellular matrix (ECM) components. Research studies to date have indicated that MMPs regulate the activity of several non-ECM bioactive substrates, including growth factors, cytokines, chemokines and cell receptors, which determine the tissue microenvironment. Disruption of the balance between the concentration of active matalloproteinases and their inhibitors (TIMPs) may lead to pathological changes associated with uncontrolled ECM turnover, tissue remodeling, inflammatory response, cell growth and migration. This brief review presents some information on MMPs' role in inflammatory, metabolic and cancer abnormalities related to the salivary glands, as well as MMP-related aspects that lead to the formation of human dentinal caries lesions. In oral diseases, the most relevant biological fluid commonly used for diagnosing periodontal diseases is saliva. In diseased patients with significantly higher levels of MMPs in their saliva than healthy people, most extracellular matrix components undergo digestion to lower molecular weight forms. Conventional treatment successfully reduces the levels of MMPs inhibits the progressive breakdown of gingival and periodontal ligament collagens. Beside inflammatory abnormalities like Sjögren's syndrome (SS), a large group of disorders is comprised of cancers, most of them involving the parotid gland (Adv Clin Exp Med 2016, 25, 2, 383-390).

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“…Examining MMP activity is significant in the diagnosis and therapy of diseases associated with MMPs -i.e., illnesses of the salivary glands and skin [34].…”

Section: Methodsmentioning

confidence: 99%

The Significance of Matrix Metalloproteinases in Oral Diseases

et al. 2015

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“…Immunochemical methods precede enzymatic methods, but cannot distinguish between active MMP and inactive MMP in zymogene form [9]. Fluorimetric methods using fluorescent-labelled substrates show low detection limits but allow to determine MMP activity quantitatively and to study target MMP sequences [10]. There are a number of other methods that are subjects of interest such as phage display, Multiple-Enzyme/Multiple-Reagent Assay System (MEMRAS) and activity-based profiling including reversed zymography.…”

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confidence: 99%

“…MMPs can be used as markers for some cancers including colorectal, thyroid, bladder and breast cancer, neurodegenerative, immune and cardiovascular diseases [8]. Assays for the detection of MMPs for both clinical and research purposes are summarized in the following reviews [9][10][11][12][13].…”

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confidence: 99%

Chip gel electrophoresis as a tool for study of matrix metalloproteinase 9 interaction with metallothionein

et al. 2011

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Matrix metalloproteinases (MMPs) play numerous roles in physiological and pathological processes including cancer. Interactions of MMPs with other zinc-binding proteins are of great interest mainly from the point of view of the participation of these proteins in carcinogenesis. The aim of this study was to utilize chip gel electrophoresis for investigation of matrix metalloproteinase 9 (gelatinase B, MMP-9) interactions with collagen. The interaction was observed and the effect of temperature was tested. We further focused on the study of activation of MMP-9 by the presence of zinc-binding proteins called metallothioneins (MT). We confirmed the basic presumption of the activation of MMP-9 by the presence of MT similar to the temperature effect. Moreover, we chose the method of differential pulse voltammetry Brdicka reaction to verify our results. It can be concluded that the activity of MMP-9 was higher in the presence of MT in comparison with the experimental collagen(type I)-MMP-9 mixture in vitro.

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“…For many MPs, the nature of the assays available limits their use for the testing of a large number of compounds because of high volume requirements, low sensitivity, and constraints of time and cost. 22 Based on our previous findings, we speculated that we could address this major issue by turning the nonspecific MP inhibitor actinonin into a universal probe for MPs. Our results show that in fact it is the case, and an FP probe based on an analog of actinonin bound to 16 of the 24 MPs tested and provided a sufficient signal window for a robust assay ( Table 2).…”

Section: Discussionmentioning

confidence: 99%

A Profiling Platform for the Identification of Selective Metalloprotease Inhibitors

2008

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Although proteases represent an estimated 5% to 10% of potential drug targets, inhibitors for metalloproteases (MPs) account for only a small proportion of all approved drugs, failures of which have typically been associated with lack of selectivity. In this study, the authors describe a novel and universal binding assay based on an actinonin derivative and show its binding activities for several MPs and its lack of activity toward all the non-MPs tested. This newly developed assay would allow for the rapid screening for inhibitors of a given MP and for the selectivity profiling of the resulting hits. The assay has successfully enabled for the first time simultaneous profiling of 8 well-known inhibitors against a panel of selected MPs. Previously published activities for these inhibitors were confirmed, and the authors have also discovered new molecular targets for some of them. The authors conclude that their profiling platform provides a generic assay solution for the identification of novel metalloprotease inhibitors as well as their selectivity profiling using a simple and homogeneous assay. (Journal of Biomolecular Screening 2008:285-294)

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Advances in assays of matrix metalloproteinases (MMPs) and their inhibitors

Cited by 29 publications

References 109 publications

The Significance of Matrix Metalloproteinases in Oral Diseases

The Significance of Matrix Metalloproteinases in Oral Diseases

Chip gel electrophoresis as a tool for study of matrix metalloproteinase 9 interaction with metallothionein

A Profiling Platform for the Identification of Selective Metalloprotease Inhibitors

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