• Title/Summary/Keyword: matrix metalloproteinases

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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 (황기, 지치 복합물의 연골세포에서의 Matrix Metalloproteinases 저해 효과 및 유효성분의 분석)

  • Choi, Doo Jin;Choi, Bo Ram;Lee, Dae Young;Choi, Soo Im;Lee, Young Seob;Kim, Geum Soog
    • Korean Journal of Medicinal Crop Science
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    • v.27 no.4
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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.

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

  • Lee, Jung-Hyun;Chang, Ju-Hea;Son, Ho-Hyun
    • Restorative Dentistry and Endodontics
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    • v.37 no.1
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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.

Expression level and glycan dynamics determine the net effects of TIMP-1 on cancer progression

  • Kim, Yong-Sam;Kim, Sun-Hee;Kang, Jeong-Gu;Ko, Jeong-Heon
    • BMB Reports
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    • v.45 no.11
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    • pp.623-628
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    • 2012
  • Tissue inhibitor of metalloproteinases (TIMPs; TIMP-1, -2, -3 and -4) are endogenous inhibitor for matrix metalloproteinases (MMPs) that are responsible for remodeling the extracellular matrix (ECM) and involved in migration, invasion and metastasis of tumor cells. Unlike under normal conditions, the imbalance between MMPs and TIMPs is associated with various diseased states. Among TIMPs, TIMP-1, a 184-residue protein, is the only N-linked glycoprotein with glycosylation sites at N30 and N78. The structural analysis of the catalytic domain of human stromelysin-1 (MMP-3) and human TIMP-1 suggests new possibilities of the role of TIMP-1 glycan moieties as a tuner for the proteolytic activities by MMPs. Because the TIMP-1 glycosylation participate in the interaction, aberrant glycosylation of TIMP-1 presumably affects the interaction, thereby leading to pathogenic dysfunction in cancer cells. TIMP-1 has not only the cell proliferation activities but also anti-oncogenic properties. Cancer cells appear to utilize these bilateral aspects of TIMP-1 for cancer progression; an elevated TIMP-1 level exerts to cancer development via MMP-independent pathway during the early phase of tumor formation, whereas it is the aberrant glycosylation of TIMP-1 that overcome the high anti-proteolytic burden. The aberrant glycosylation of TIMP-1 can thus be used as staging and/or prognostic biomarker in colon cancer.

Purification of Progelatinase A (Matrix Metalloproteinase 2) and a Tissue Inhibitor of Metalloproteinase-2(TIMP-2) from T98G Human Glioblastoma Cells

  • Lee, Ho-Jae;Chung, Myung-Chul;Lee, Choong-Hwan;Chun, Hyo-Kon;Kho, Yung-Hee
    • BMB Reports
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    • v.28 no.1
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    • pp.33-39
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    • 1995
  • The Gelatinases (typeIV collagenases) are metalloproteinases that may play an important role in tumor invasion and metastasis. Progelatinase A was purified from a conditioned medium of T98G human glioblastoma cells. TIMP-2 complexed progelatinase A and free progelatinase A were separated by heparin affinity HPLC. The final product was homogeneous on SDS-PAGE, with a molecular weight of 64,000 daltons without reduction. TIMP-2 and free progelatinase A were separated from TIMP-2 complexed progelatinase A by reverse-phase HPLC in the presence of trifluoroacetic acid. TIMP-2 complexed progelatinase A was resistant to activation by p-aminophenyl mercuric acetate (APMA), and showed less than 20% of the activity of the TIMP-2 free active enzyme. TIMP-2 free progelatinase A was easily activated to the mature form with a molecular weight of 57,000 daltons by APMA and showed high activity compared to the TIMP-2 complexed enzyme.

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Protective effects of red orange (Citrus sinensis [L.] Osbeck [Rutaceae]) extract against UVA-B radiation-induced photoaging in Skh:HR-2 mice

  • Yoon Hee Kim;Cho Young Lim;Jae In Jung ;Tae Young Kim;Eun Ji Kim
    • Nutrition Research and Practice
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    • v.17 no.4
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    • pp.641-659
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    • 2023
  • BACKGROUND/OBJECTIVES: The skin is the outermost organ of the human body and plays a protective role against external environmental damages, such as sunlight and pollution, which affect anti-oxidant defenses and skin inflammation, resulting in erythema or skin reddening, immunosuppression, and epidermal DNA damage. MATERIALS/METHODS: The present study aimed to investigate the potential protective effects of red orange complex H extract (ROC) against ultraviolet (UV)-induced skin photoaging in Skh:HR-2 mice. ROC was orally administered at doses of 20, 40, and 80 mg/kg/day for 13 weeks, along with UV irradiation of the mice for 10 weeks. RESULTS: ROC improved UV-induced skin barrier parameters, including erythema, melanin production, transepidermal water loss, elasticity, and wrinkle formation. Notably, ROC inhibited the mRNA expression of pro-inflammatory cytokines (interleukin 6 and tumor necrosis factor α) and melanogenesis. In addition, ROC recovered the UV-induced decrease in the hyaluronic acid and collagen levels by enhancing genes expression. Furthermore, ROC significantly downregulated the protein and mRNA expression of matrix metalloproteinases responsible for collagen degradation. These protective effects of ROC against photoaging are associated with the suppression of UV-induced phosphorylation of c-Jun NH2-terminal kinase and activator protein 1 activation. CONCLUSIONS: Altogether, our findings suggest that the oral administration of ROC exerts potential protective activities against photoaging in UV-irradiated hairless mice.

The Relation of Residual Pleural Thickening with Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases of Pleural Effusion in Patients with Tuberculous Pleuritis (결핵성 흉막염 환자에서 흉수 내 Matrix Metalloproteinases 및 Tissue Inhibitors of Metalloproteinases 농도와 잔여 흉막비후와의 관계)

  • Choi, Youngkwon;An, Chang Hyeok;Kim, Yu Jin;Kyung, Sun Young;Lee, Sang Pyo;Park, Jeong Woong;Jeong, Sung Hwan
    • Tuberculosis and Respiratory Diseases
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    • v.65 no.1
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    • pp.7-14
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    • 2008
  • Background: Residual pleural thickening (RPT) is the most frequent complication of tuberculous pleurisy (TP), and this can happen despite of administering adequate anti-tuberculous (TB) therapy. Yet there was no definite relation between RPT and other variables. The aim of this study was to examine matrix metalloproteinases (MMPs) and the inhibitors of metalloproteinases (TIMPs) and to identify the factors that can predict the occurrence of RPT. Methods: The patients with newly-detected pleural effusions were prospectively enrolled in this study from January 2004 to June 2005. The levels of MMP-1, -2, -8 and -9, and TIMP-1 and -2 were determined in the serum and pleural fluid by ELISA. The residual pleural thickness was measured at the completion of treatment and at the point of the final follow-up with the chest X-ray films. Results: The study included 39 patients with pleural fluid (PF). Twenty-three had tuberculous effusion, 7 had parapneumonic effusion, 7 had malignant effusion and 2 had transudates. For the 17 patients who completed the anti-TB treatment among the 23 patients with TP, 7 (41%) had RPT and 10 (59%) did not. The level of PF TIMP-1 in the patients with RPT ($41,405.9{\pm}9,737.3ng/mL$) was significantly higher than that of those patients without RPT ($29,134.9{\pm}8,801.8$) at the completion of treatment (p=0.032). In 13 patients who were followed-up until a mean of $8{\pm}5$ months after treatment, 2 (15%) had RPT and 11 (85%) did not. The level of PF TIMP-2 in the patients with RPT ($34.4{\pm}6.5ng/mL$) was lower than that of those patients without RPT ($44.4{\pm}15.5$) at the point of the final follow-up (p=0.038). Conclusion: The residual pleural thickening in TP might be related to the TIMP-1 and TIMP-2 levels in the pleural fluid.

Inhibition of Matrix Metalloproteinase-2 Activity of Flavonol Glycosides from Cedreia sinensis (참죽나무에서 분리한 flavonol glycoside의 금속단백분해효소-2 억제 활성)

  • Hwang Seon-Woo;Ha Tae-Joung;Kho Yung-Hee;Chun Hyo-Kon;Lee Jun;Kwon Hyun-Sook;Park Ki-Hun;Yang Min-Suk
    • Journal of Life Science
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    • v.16 no.3 s.76
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    • pp.442-446
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    • 2006
  • Cedrela sinensis is a broadleaf tree that is widely cultivated in Korea and China. It was used for treating enteritis, dysentery, and skin itch in oriental medicine. In this study, three major flavonoids, kaempferol-3-O-rhamnoside (1), quercetin-3-O-rhamnoside (2), and quercetin-3-O-glucoside (3), were isolated from the leaf of Cedrela sinensis. The biological activities of these compounds were tested by inhibitory activity of matrix metalloproteinases-2 (Type IV collagenase) method together with a cytotoxicity and a apoptosis test against human cancer cell lines.

Effect of red ginseng NaturalGEL on skin aging

  • Kim, Ye Hyang;Park, Hye Rim;Cha, So Yoon;Lee, So Hun;Jo, Jung Wung;Go, Jung Nam;Lee, Kang Hyuk;Lee, Su Yeon;Shin, Song Seok
    • Journal of Ginseng Research
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    • v.44 no.1
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    • pp.115-122
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    • 2020
  • Background: In aged skin, degradation of collagen fibers, which occupy the majority of the extracellular matrix in the dermis, and changes of aquaporin 3 (AQP3) and skin constituents, such as hyaluronic acid and ceramide, cause wrinkles and decrease skin moisturization to contribute to dryness and lower elasticity skin. Red ginseng (RG) is used as a cosmetic and food material and is known to protect from UVB-induced cell death, increase skin hydration, prevent wrinkles, and have an antioxidative effect. But, in general, RG used as a material is the soluble liquid portion in the solvent, and the part that is not soluble in the solvent is discarded. Thus, we made the whole RG into microgranulation and dispersed in water to produce gel form for using entire RG, and it was named red ginseng NaturalGEL (RG NGEL). Methods: RG NGEL was investigated for matrix metalloproteinases inhibitory activity, induction of Type I collagen, AQP3, hyaluronan synthetase 2, serine palmitoyl transferase, ceramide synthase 3, and filaggrin expression and compared with RG water extract. Results: RG NGEL reduced the levels of UV-induced matrix metalloproteinases and increased Type I collagen in human fibroblast cells and upregulated AQP3, hyaluronan synthetase 2, serine palmitoyl transferase, ceramide synthase 3, and filaggrin expressions in human keratinocytes compared with RG water extract. Conclusion: RG NGEL has the potential as an effective reagent for antiaging cosmetics to improve wrinkle formation and skin hydration.

Inhibitory Effect of Rosa multiflora hip Extract on UVB-induced Skin Photoaging in Hs68 Fibroblasts (자외선으로 유도된 Hs68 섬유아세포의 노화 반응에 대한 영실추출물의 억제 효능)

  • Park, Ji-Eun;Kim, Hyoung Ja;Kim, Su-Nam;Kang, Seung Hyun;Kim, Youn Joon
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.41 no.4
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    • pp.351-359
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    • 2015
  • Acute and chronic ultraviolet (UV) irradiation triggers severe skin photoaging processes, which directly disrupt the normal three-dimensional integrity of skin. UV light stimulates the expression of matrix metalloproteinases (MMPs) which degrade constituents of extracellular matrix (ECM) proteins. These MMPs reduce collagen synthesis and decrease skin elasticity and integrity, resulting in wrinkle formation. In this study, we identified Rosa multiflora hip extract (RME) as an effective anti-photoaging ingredient. First, cell proliferation activity of RME was verified using Hs68 human dermal fibroblast cell line. RME downregulated MMPs expression through the inhibition of activator protein (AP)-1. In addition, type I and IV collagen expressions were increased with RME treatment and UVB-induced inflammatory responses were also reduced after RME treatment. In conclusion, R. multiflora hip extract may effectively improve UVB-induced skin aging and wrinkle formation which may provide as an anti-aging, anti-wrinkle, and anti-inflammation ingredient in cosmetic industry.

Fluorescent and bioluminescent nanoprobes for in vitro and in vivo detection of matrix metalloproteinase activity

  • Lee, Hawon;Kim, Young-Pil
    • 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]