• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1085-1091
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• 2014

Matrix metalloproteinases (MMPs) are a family of zinc dependent extracellular matrix (ECM) remodelling endopeptidases having the ability to degrade almost all components of extracellular matrix and implicated in various physiological as well as pathological processes. Carcinogenesis is a multistage process in which alteration of the microenvironment is required for conversion of normal tissue to a tumour. Extracellular matrix remodelling proteinases such as MMPs are principal mediators of alterations observed in the microenvironment during carcinogenesis and according to recent concepts not only have roles in invasion or late stages of cancer but also in regulating initial steps of carcinogenesis in a favourable or unfavourable manner. Establishment of relationships between MMP overproduction and cancer progression has stimulated the development of inhibitors that block proteolytic activity of these enzymes. In this review we discuss the MMP general structure, classification, regulation roles in relation to hallmarks of cancer and as targets for therapeutic intervention.

• YAKHAK HOEJI
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• v.38 no.5
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• pp.530-543
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• 1994

To study the feasibility of transmucosal delivery of leucine enkephalin (Leu-Enk) and $[D-ala^2]$-leucine enkephalinamide (YAGFL), their degradation extents and pathways in various rabbit mucosa extracts were investigated by high performance liquid chromatography. The degradation of Leu-Enk and YAGFL was observed to follow the first-order kinetics. The degradation half-lives of Leu-Enk in the nasal, rectal and vaginal mucosal extracts were 1.62, 0.37 and 1.12 hrs and those of YAGFL were 30.55, 9.70 and 6.82 hrs, respectively, indicating Leu-Enk was degraded in a more extensive and rapid manner than YAGFL. But the mucosal and serosal extracts of the same mucosa showed the similar degradation rates for both pentapeptides. The degradation was most rapid in the neutral pH and increasing concentrations of substrates retarded the degradation rates. The maior hydrolytic fragments of Leu-Enk were Des-Tyr-Leu-Enk and tyrosine, indicating the enzymatic hydrolysis by aminopeptidases. However, the data also suggested endopeptidases such as dipeptidyl carboxypeptidase and dipeptidyl aminopeptidase could play some role in the degradation of Leu-Enk. On the other hand, the hydrolytic fragments of YAGFL in all the mucosa extracts were mainly Tyr-D-Ala-Gly and Phe-Leu-Amide, demonstrating the hydrolytic breakdown by endopeptidases. The degradation pathways were further explored by concomitantly determining the formation of smaller metabolites of primary hydrolytic fragments of Leu-Enk and YAGFL in the mucosa extracts.

• BMB Reports
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• v.48 no.6
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• pp.313-318
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• 2015

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that degrade the extracellular matrix (ECM) and regulate the extracellular microenvironment. Despite the significant role that MMP activity plays in cell-cell and cell-ECM interactions, migration, and differentiation, analyses of MMPs in vitro and in vivo have relied upon their abundance using conventional immunoassays, rather than their enzymatic activities. To resolve this issue, diverse nanoprobes have emerged and proven useful as effective activity-based detection tools. Here, we review the recent advances in luminescent nanoprobes and their applications in in vitro diagnosis and in vivo imaging of MMP activity. Nanoprobes with the purpose of sensing MMP activity consist of recognition and detection units, which include MMP-specific substrates and luminescent (fluorescent or bioluminescent) nanoparticles, respectively. With further research into improvement of the optical performance, it is anticipated that luminescent nanoprobes will have great potential for the study of the functional roles of proteases in cancer biology and nanomedicine. [BMB Reports 2015; 48(6): 313-318]

• Genomics & Informatics
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• v.14 no.1
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• pp.12-19
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• 2016

Neuropeptides produced from prohormones by selective action of endopeptidases are vital signaling molecules, playing a critical role in a variety of physiological processes, such as addiction, depression, pain, and circadian rhythms. Neuropeptides bind to post-synaptic receptors and elicit cellular effects like classical neurotransmitters. While each neuropeptide could have its own biological function, mass spectrometry (MS) allows for the identification of the precise molecular forms of each peptide without a priori knowledge of the peptide identity and for the quantitation of neuropeptides in different conditions of the samples. MS-based neuropeptidomics approaches have been applied to various animal models and conditions to characterize and quantify novel neuropeptides, as well as known neuropeptides, advancing our understanding of nervous system function over the past decade. Here, we will present an overview of neuropeptides and MS-based neuropeptidomic strategies for the identification and quantitation of neuropeptides.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3043-3051
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• 2016

Controlled remodeling of the extracellular matrix (ECM) is essential for cell growth, invasion and metastasis. Matrix metalloproteinases (MMPs) are a family of secreted, zinc-dependent endopeptidases capable of degradation of ECM components. The expression and activity of MMPs in a variety of human cancers have been intensively studied. They play important roles at different steps of malignant tumor formation and have central significance in embryogenesis, tissue remodeling, inflammation, angiogenesis and metastasis. However, increasing evidence demonstrates that MMPs are involved earlier in tumorigenesis. Recent studies also suggest that MMPs play complex roles in tumor progression. MMPs and membrane type (MT)-MMPs are potentially significant therapeutic targets in many cancers, so that designing of specific MMP inhibitors would be helpful for clinical trials. Here, we review the pleiotropic roles of the MMP system in hematological malignancies in-vitro and in-vivo models.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7393-7400
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• 2015

Matrix metalloproteinase (MMP) 9, a key member of multifunctional family of zinc dependent endopeptidases has been found to be upregulated during inflammation and in some cancers. MMPs cleave extracellular matrix (ECM) proteins and play critical roles in cellular apoptosis, angiogenesis, tumor growth and metastasis. Several genetic polymorphisms have been identified that show allele specific effects on MMP9 regulation and are associated with gastric cancer, the fourth most common malignancy in the world. Besides Helicobacter pylori infection, genetic predisposition is another documented risk factor for gastric carcinoma. The single nucleotide polymorphism (SNP) at position -1562C/T of MMP9 results in the modulation for binding of transcription factors to the MMP9 gene promoter and thereby causes differences in protein expression and enzymatic activity. MMP9 transcriptional regulation during gastric cancer development remains poorly known although several studies have demonstrated associations between MMP9 -1562 C/T polymorphism with different diseases. Knowledge on mechanisms of MMP9 upregulation during gastric cancer may provide new paradigm in diagnostics and therapeutics.

• BMB Reports
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• v.43 no.1
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• pp.62-68
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• 2010

Matrix Metalloproteinases (MMPs) are a family of zinc-endopeptidases which can degrade extracellular matrix (ECM) components and play important roles in a variety of biological and pathological processes. 6,6'-bieckol isolated and characterized from an edible marine brown alga Ecklonia cava (EC), according to the comprehensive spectral analysis of MS and NMR data. Here the influence of 6,6'-bieckol on expressions of MMPs was examined by zymography and western blot analysis via human fibrosarcoma cell line (HT1080). It is shown that 6,6'-bieckol significantly down regulated the expressions of MMP-2 and -9 in dose-dependent manner. The influence of 6,6'-bieckol on the cell viability and cell behavior of HT1080 cells were also investigated, our dates shown that it suppressed the migration and 3D culture in HT1080 cells. Meanwhile, we explored several signal pathways which may contribute to this process, and found the suppressing of MMPs expressions in HT1080 cells might be due to the suppression of NF-${\kappa}B$ signal pathway.

• Preventive Nutrition and Food Science
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• v.22 no.3
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• pp.184-190
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• 2017

Matrix metalloproteinases (MMPs) are endopeptidases that take significant roles in extracellular matrix degradation and therefore linked to several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Hizikia fusiformis, a brown algae, was reported to possess bioactivities, including but not limited to, antiviral, antimicrobial, and anti-inflammatory partly due to bioactive polysaccharide contents. In this study, the potential of H. fusiformis against cancer cell invasion was evaluated through the MMP inhibitory effect in HT1080 fibrosarcoma cells in vitro. H. fusiformis crude extract was fractionated with organic solvents, $H_2O$, n-BuOH, 85% aqueous MeOH, and n-hexane (n-Hex). The non-toxicity of the fractions was confirmed by MTT assay. All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to the gelatin zymography assay. Cell migration was also significantly inhibited by the n-Hex fraction. In addition, both gene and protein expressions of MMP-2 and -9, and tissue inhibitor of MMPs (TIMPs) were evaluated by reverse transcription-polymerase chain reaction and Western blotting, respectively. The fractions suppressed the mRNA and protein levels of MMP-2, MMP-9 while elevating the TIMP-1 and TIMP-2, with the $H_2O$ fraction being the least effective while n-Hex fraction the most. Collectively, the n-Hex fraction from brown algae H. fusiformis could be a potential inhibitor of MMPs, suggesting the presence of various derivatives of polysaccharides in high amounts.

• Parasites, Hosts and Diseases
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• v.30 no.3
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• pp.191-200
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• 1992

A proteolytic enzyme was purified from the tissue extract of spargana (plerocercoids of Spirometra erinacei) by DEAE-Trisacryl M ion exchange chromatography and thiopropyl-sepharose affinity chromatography resulted in a 21-fold purification. The proteinase activity was assayed with a synthetic fluorescent substrate, carbobensoxy-phenylalanyl-7-amiso-4-trifluoromethyl-coumarin. SDS-polyacplamide gel electrophoresis of the purified materials revealed a single 28,000 dalton band. Inhibitor profiles of the band indicated that it belonged to cysteine endopeptidases. It exhibited identical pH curves with optimum at pH 5,5, and 50% activity from pH 4.7 to 8. It could completely degrade collagen chains to three identical products. It also showed some activity on hemoglobin. Furthermore, the band on immunoblots was reactive to the sera of sparganosis patients. These results suggest that the proteolytic enzyme belongs to cysteine proteinase which plays a role in the tissue penetration. Also it may be used as the antigen for diagnosis of active sparganosis.

• Journal of Plant Biotechnology
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• v.31 no.4
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• pp.313-317
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• 2004

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases produced by a variety of cell type, and have a fundamental role in the degradation and remodeling of extracellular matrix. In this study, we screened the secretion of MMPs in leaves of different developmental stages and in response to environmental stress using tobacco. Compare with fully maturing leaves and older leaves, the rate of MMPs activity was high in expanding and younger leaves. It is tempting to speculate that MMPs may be involved in tissue modeling, which must occur during leaf expansion. The MMPs activity in tobacco leaves grown in the presence of stressors showed a significantly increase at salinity treatment and pathogen infection. The MMPs activity in salinity and pathogen treatment increased respectively, by 1.2- and 1.5-fold with respect to the control. These results suggest that MMPs may be involved in plant defence against adverse environment and pathogenic infection.