• 제목/요약/키워드: matrix metalloproteinases (MMPs)

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두툽상어 matrix metalloproteinase 유전자 cDNA의 클로닝 (Cloning of a matrix metalloproteinase cDNA from Scylliorhinus torazame)

  • 김종원;조원진;천광호;김규원;김영진;이상준;신혜자;임운기
    • 생명과학회지
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    • 제8권3호
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    • pp.235-240
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    • 1998
  • Matrix metalloproteinases(MMP)는 배발생 및 재조직화 등의 정상적인 생체형성과 관절염, 암전이, 치근막염, 골조송증 등의 질병과정에서 collagen이나 proteoglycan과 같은 세포외기질의 구성성분을 분해하는 아연(zinc)효소군이다. 지금까지 다양한 종에서 mmp의 유전자가 클로닝되고 그 기능이 연구되어 왔지만 아직 어류에서는 연구결과가 보고된 바가 없다. 본 연구에서는 한국의 부산연안에 많은 연골어유 투툽상어(Scylliorhinus toraxzame)로부터 RT-PCR(reverse transcriptase dependent polymerase chain reaction)의방법으로 mmp cDNA의 일부를 클로닝하였다. 이것은 염기서열에서 인간, 쥐 및 닭의 membrane type matrix matalloproteinase-3(mt3-mmps)의 염기서열과 74% 동일성을 보이며, 아미노산서열에서는 90%이상의 동일성을 갖고 있다. 또한 MMP에 나타나는 cysteine switch domain, zinc binding domain(HExGH motif), propeptide cleavage site, and RRKR motif등을 가지고 있다. 이러한 결과로부터 본 연구에서 클로닝된 RT-PCR단편은 두툽상어의 mt3-mmp 또는 이와 유사한 유전자의 cDNA이라 믿어진다.

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Inhibition of the expression on MMP-2, 9 and morphological changes via human fibrosarcoma cell line by 6,6'-bieckol from marine alga Ecklonia cava

  • Zhang, Chen;Li, Yong;Shi, Xiujuan;Kim, Se-Kwon
    • BMB Reports
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    • 제43권1호
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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.

Prevotella intermedia의 세균내독소가 치은섬유아세포와 치주인대세포에서의 matrix metalloproteinase 및 tissue inhibitor of metalloproteinase의 발현에 미치는 영향 (Expression of mRNA for matrix metalloproteinases and tissue inhibitors of metalloproteinases in human gingival and periodontal ligament fibroblasts treated with lipopolysaccharide from Prevotella intermedia)

  • 김성조;최은영;최인순;이주연;최점일;김종관
    • Journal of Periodontal and Implant Science
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    • 제35권1호
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    • pp.21-30
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    • 2005
  • Matrix metalloproteinases (MMPs) are a family of host-derived proteolytic enzymes and implicated in the remodeling and degradation of extracellular matrix under both physiological and pathological conditions. Connective tissue degradation in periodontal diseases is thought to be due to excessive MMP activities over their specific inhibitors. The effects of lipopolysaccharide (LPS) from Prevotella intermedia, one of the major putative pathogens of periodontitis, on the expression of mRNA for MMPs and tissue inhibitors of metalloproteinases (TIMPs) in human gingival and periodontal ligament fibroblasts were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of mRNAs encoding MMP-1, -2, -3, -10, and -14 was increased in human gingival fibroblasts treated with p. intermedia LPS, whereas MMP-11 and TIMP-2 mRNA expression was decreased in these cells stimulated with LPS. P. intermedia LPS increased the MMP-1, -2, -10, -11, and -14 mRNA expression and decreased TIMP-1 and -2 mRNA expression in human periodontal ligament fibroblasts. These findings imply that P. intermedia LPS may play an important role in the connective tissue degradation in periodontitis.

상아질 접착에 대한 matrix metalloproteinase (MMP)의 영향과 이를 극복하기 위한 전략 (Effects of matrix metallproteinases on dentin bonding and strategies to increase durability of dentin adhesion)

  • 이정현;장주혜;손호현
    • Restorative Dentistry and Endodontics
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    • 제37권1호
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    • pp.2-8
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    • 2012
  • The limited durability of resin-dentin bonds severely compromises the longevity of composite resin restorations. Resin-dentin bond degradation might occur via degradation of water-rich and resin sparse collagen matrices by host-derived matrix metalloproteinases (MMPs). This review article provides overview of current knowledge of the role of MMPs in dentin matrix degradation and four experimental strategies for extending the longevity of resin-dentin bonds. They include: (1) the use of broadspectrum inhibitors of MMPs, (2) the use of cross-linking agents for silencing the activities of MMPs, (3) ethanol wet-bonding with hydrophobic resin, (4) biomimetic remineralization of water-filled collagen matrix. A combination of these strategies will be able to overcome the limitations in resin-dentin adhesion.

Matrix Metalloproteinases and Cancer - Roles in Threat and Therapy

  • Yadav, Lalita;Puri, Naveen;Rastogi, Varun;Satpute, Pranali;Ahmad, Riyaz;Kaur, Geetpriya
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권3호
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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.

Diphlorethohydroxycarmalol Suppresses Ultraviolet B-Induced Matrix Metalloproteinases via Inhibition of JNK and ERK Signaling in Human Keratinocytes

  • Piao, Mei Jing;Kumara, Madduma Hewage Susara Ruwan;Kim, Ki Cheon;Kang, Kyoung Ah;Kang, Hee Kyoung;Lee, Nam Ho;Hyun, Jin Won
    • Biomolecules & Therapeutics
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    • 제23권6호
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    • pp.557-563
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    • 2015
  • Skin aging is the most readily observable process involved in human aging. Ultraviolet B (UVB) radiation causes photo-oxidation via generation of reactive oxygen species (ROS), thereby damaging the nucleus and cytoplasm of skin cells and ultimately leading to cell death. Recent studies have shown that high levels of solar UVB irradiation induce the synthesis of matrix metalloproteinases (MMPs) in skin fibroblasts, causing photo-aging and tumor progression. The MMP family is involved in the breakdown of extracellular matrix in normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as arthritis and metastasis. We investigated the effect of diphlorethohydroxycarmalol (DPHC) against damage induced by UVB radiation in human skin keratinocytes. In UVB-irradiated cells, DPHC significantly reduced expression of MMP mRNA and protein, as well as activation of MMPs. Furthermore, DPHC reduced phosphorylation of ERK and JNK, which act upstream of c-Fos and c-Jun, respectively; consequently, DPHC inhibited the expression of c-Fos and c-Jun, which are key components of activator protein-1 (AP-1, up-regulator of MMPs). Additionally, DPHC abolished the DNA-binding activity of AP-1, and thereby prevented AP-1-mediated transcriptional activation. These data demonstrate that by inactivating ERK and JNK, DPHC inhibits induction of MMPs triggered by UVB radiation.

Effects of Hormones on the Expression of Matrix Metalloproteinases and Their Inhibitors in Bovine Spermatozoa

  • Kim, Sang-Hwan;Song, Young-Seon;Hwang, Sue-Yun;Min, Kwan-Sik;Yoon, Jong-Taek
    • Asian-Australasian Journal of Animal Sciences
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    • 제26권3호
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    • pp.334-342
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    • 2013
  • Proteases and protease inhibitors play key roles in most physiological processes, including cell migration, cell signaling, and cell surface and tissue remodeling. Among these, the matrix metalloproteinase (MMPs) pathway is one of the most efficient biosynthetic pathways for controlling the activation of enzymes responsible for protein degradation. This also indicates the association of MMPs with the maturation of spermatozoa. In an attempt to investigate the effect of MMP activation and inhibitors in cultures with various hormones during sperm capacitation, we examined and monitored the localization and expression of MMPs (MMP-2 and MMP-9), tissue inhibitors of metalloproteinases (TIMP-2 and TIMP-3), as well as their expression profiles. Matured spermatozoa were collected from cultures with follicle-stimulating hormone (FSH), luteinizing hormone (LH), and Lutalyse at 1 h, 6 h, 18 h, and 24 h. ELISA detected the expression of MMP-2, MMP-9, TIMP-2, and TIMP-3 in all culture media, regardless of medium type (FSH-supplemented fertilization Brackett-Oliphant medium (FFBO), LH-supplemented FBO (LFBO), or Lutalyse-supplemented FBO (LuFBO)). TIMP-2 and TIMP-3 expression patterns decreased in LFBO and LuFBO. MMP-2 and MMP-9 activity in FBO and FFBO progressively increased from 1 h to 24 h but was not detected in LFBO and LuFBO. The localization and expression of TIMP-2 and TIMP-3 in sperm heads was also measured by immunofluorescence analysis. However, MMPs were not detected in the sperm heads. MMP and TIMP expression patterns differed according to the effect of various hormones. These findings suggest that MMPs have a role in sperm viability during capacitation. In conjunction with hormones, MMPs play a role in maintaining capacitation and fertilization by controlling extracellular matrix inhibitors of sperm.

동결융해 후 토끼 정자의 Matrix Metalloproteinases (MMPs)와 Their Tissue Inhibitors (TIMPs) 발현 양상 (Expression of Matrix Metalloproteinases (MMPs) and Their Tissue Inhibitors (TIMPs) in Frozen Sperm of Rabbit)

  • 김상환;최화식;윤종택
    • 한국동물생명공학회지
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    • 제34권3호
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    • pp.247-252
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    • 2019
  • We observed MMPs expression in all sperm groups, with pro-MMP showing lower expression than active MMPs. According to the results from each freezing extender, the sperm membrane integrity (HOST: Hypoosmotic Swelling Test) analysis in TCGGD (Tris 250 mM, Citric acid 88 mM, Glucose 47 mM, Glycerol 3%, Dimethylsulpoxide 3.5 M) is 59.8 ± 0.7, TCGSD (Tris 250 mM, Citric acid 88 mM, Glucose 47 mM, Sucrose 0.1 M, Dimethylsulpoxide 3.5 M) is 59.3 ± 0.5 were significantly higher (p < 0.05) among the experimental groups. And MMPs analysis result, we observed MMPs expression in all sperm groups, with pro-MMP showing lower expression than active MMPs. The expression of active MMP-2 was the highest in sperms frozen in TCGSD and TCGD (Tris 250 mM, Citric acid 88 mM, Glucose 47 mM, Dimethylsulpoxide 3.5 M), Meanwhile, sperms from the TCGGD and TCGED (Tris 250 mM, Citric acid 88 mM, Glucose 47 mM, Ethylene glycol 3%, Dimethylsulpoxide 3.5 M) group showed lower level of active MMP-2 expression. Together, these results indicate that adding glycerol or sucrose to the sperm freezing buffer would not only suppress MMPs expression but also minimize DNA fragmentation, providing a mean to improve the success rate in the in vitro manipulation of rabbit sperms. Therefore, these results suggest that TCGGD or TCGSD extender method for freezing-thawing of rabbit sperm increased the viability after thawing.

Peptide Hydrolysates from Astragalus membranaceus Bunge Inhibit the Expression of Matrix Metalloproteinases in Human Dermal Fibroblasts

  • Park, Sun Ki;Van Hien, Pham;Van Luong, Hoang;Yan, Shao-Wei;Byun, Sang Yo
    • KSBB Journal
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    • 제29권5호
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    • pp.380-384
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    • 2014
  • Inhibition effects of peptide hydrolysates from Astragalus membranaceus Bunge. on the expression of the matrix metalloproteinases (MMPs) in human dermal fibroblasts were evaluated in vitro. Crude peptides were obtained by the hydrolysis of proteins extracted from A. membranaceus. Peptides were purified partially by the basis on the molecular weight using 40% polyacrylamide gel electrophoresis before treatment with human dermal fibroblasts. Basis on the doseeffect experiments, expressions of MMPs including MMP-1, MMP-3, MMP-8, MMP-13 in human dermal fibroblasts were evaluated. Expressions of MMP-1, MMP-3, MMP-8 and MMP-13 were reduced in 43%, 5%, 22% and 57% respectively. The mass spectrometric analysis of partially purified peptides from A. membranaceus, which strongly inhibit expressions of MMPs, indicated that the peptides were composed of molecules below 1500 Da.

황기, 지치 복합물의 연골세포에서의 Matrix Metalloproteinases 저해 효과 및 유효성분의 분석 (Inhibitory Effect of Mixed Extracts Obtained from Astragali Radix and Lithospermi Radix on Matrix Metalloproteinases in IL-1β-induced SW1353 Cells and Quantitative Analysis of Active Compounds)

  • 최두진;최보람;이대영;최수임;이영섭;김금숙
    • 한국약용작물학회지
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    • 제27권4호
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    • pp.247-258
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    • 2019
  • Background: Astragali radix (A) and Lithospermi radix (L) have long been used as traditional medicines due to their known anti-inflammatory effects. This study aimed at evaluating, their optimal mixing ratio and their functional compounds by investigating the inhibitory effects of mixed extracts of A and L and their active compounds on matrix metalloproteinases (MMPs). Methods and Results: A and L extracts were obtained by extraction at $80^{\circ}C$ using 50% and 70% fermented alcohol, respectively, and then mixed at a ratio of 5 : 5, 6 : 4, 7 : 3 and 8 : 2 (w/w). The activities of MMP-1, MMP-3, and MMP-13 were evaluated in interleukin-1beta ($IL-1{\beta}$)-induced SW1353 cells. The extract mixtures showed synergistic inhibitory effects on MMP-3 and MMP-13, higher than the effects of the individual A and L extracts. The 7 : 3 mixture (ALM16) showed the most effective MMPs inhibitory activity, while among the active ingredients, calycosin-7-O-${\beta}$-D-glucoside and lithospermic acid exhibited excellent MMPs inhibitory activity. Additionally, an HPLC method was established for simultaneous quantification of the effective components of the extract mixtures, and validated by measuring the linearity, precision and accuracy of the limit of detection (LOD) and limit of quantification (LOQ). Conclusions: ALM16 showed the most effective MMPs inhibitory activity. Calycosin-O-${\beta}$-D-glucoside, calycosin and lithospermic acid were identified as useful candidates, as they were the major functional compounds in the MMP inhibitory activity. Summarily, ALM16 might be a highly effective in osteoarthritis management, owing to its because it exhibits a protective effect on cartilage via excellent inhibition of MMPs.