• Title/Summary/Keyword: Matrix metalloproteinase-1

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Antioxidant and Metalloproteinase Inhibitory Activities of Ethanol Extracts from Lespedeza cuneata G. Don (야관문 에탄올 추출물의 항산화 및 Metalloproteinase 저해 활성)

  • Shin, Yong Ha;Song, Chang-Khil
    • Korean Journal of Environmental Agriculture
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    • v.36 no.4
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    • pp.263-268
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    • 2017
  • BACKGROUND: Lespedeza cuneata G. Don is a well-known medicinal plant. In this study, the biological activities of L. cuneata extracts were investigated. METHODS AND RESULTS: L. cuneata shoot was extracted with 30% ethanol and further fractionated with organic solvents. Total phenolic and flavonoid content, antioxidant activity, and matrix metalloproteinase inhibition effect of the extract and fractions were measured. Among the tested extract and fractions, the highest contents of total phenolic and flavonoids were found in ethyl acetate fraction (117.8 mg GAE/g and 35.9 mg QE/g, respectively). Ethyl acetate fraction showed the highest DPPH and ABTS radical scavenging activity, and the antioxidant activity of the other fractions followed the order n-hexane fraction>ethanol extract>methyl chloroform>n-butanol fraction. Inhibitory effect on the expression of matrix metalloproteinases (MMP1 and MMP3) was highest in the fraction of ethyl acetate, and n-butanol fraction also significantly inhibited the expression of MMP3. Antioxidant activities of L. cuneata extracts were significantly positively related to their phenolic and flavonoid content. CONCLUSION: Ethyl acetate fraction of L. cuneata ethanol extract showed potent antioxidant and matrix metalloproteinases inhibitory activities. Those activities might be related to the high total phenolic and flavonoid content of the extract.

Baicalein Attenuates Oxidative Stress-Induced Expression of Matrix Metalloproteinase-1 by Regulating the ERK/JNK/AP-1 Pathway in Human Keratinocytes

  • Kim, Ki-Cheon;Kang, Sam-Sik;Lee, Jong-Sung;Park, Deok-Hoon;Hyun, Jin-Won
    • Biomolecules & Therapeutics
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    • v.20 no.1
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    • pp.57-61
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    • 2012
  • The matrix metalloproteinase (MMP) family is involved in the breakdown of the extracellular matrix during normal physiological processes such as embryonic development, reproduction, and tissue remodeling, as well as in disease processes such as pathological aging, arthritis, and metastasis. Oxidative conditions generate reactive oxygen species (ROS) (e.g., hydrogen peroxide [$H_2O_2$]) in cells, which subsequently induce the synthesis of matrix metalloproteinase-1 (MMP-1). MMP-1, an interstitial collagenase, in turn stimulates an aging phenomenon. In this study, baicalein (5,6,7-trihydroxyfl avone) was investigated for its in vitro activity against $H_2O_2$-induced damage using a human skin keratinocyte model. Baicalein pretreatment signifi cantly inhibited $H_2O_2$-induced up-regulation of MMP-1 mRNA, MMP-1 protein expression and MMP-1 activity in cultured HaCaT keratinocytes. In addition, baicalein decreased the transcriptional activity of activator protein-1 (AP-1) and the expression of c-Fos and c-Jun, both components of the heterodimeric AP-1 transcription factor. Furthermore, baicalein reduced phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun-N-terminal kinase (JNK), which are upstream of the AP-1 transcription factor. The results of this study suggest that baicalein is involved in the inhibition of oxidative stress-induced expression of MMP-1 via inactivation of the ERK/JNK/AP-1 signaling pathway.

Caveolin-1 inhibits membrane-type 1 matrix metalloproteinase activity

  • Kim, Hye-Nan;Chung, Hye-Shin
    • BMB Reports
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    • v.41 no.12
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    • pp.858-862
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    • 2008
  • Membrane-type 1 matrix metalloproteinase (MT1-MMP) is a zinc-dependent proteinase found in cholesterol-rich lipid rafts on the plasma membrane. MT1-MMP hydrolyzes extracellular matrix (ECM) proteins, activates pro-matrix metalloproteinase-2 (proMMP-2) and plays an important role in ECM remodeling, cancer cell migration and metastasis. The role of caveolin-1, an integral protein of caveolae, in the activation of MT1-MMP remains largely unknown. Here, we show that the expression of caveolin-1 attenuates the activation of proMMP-2, reduces proteolytic cleavage of ECM and inhibits cell migration. We utilized the cytoplasmic tail domain deletion (${\Delta}CT$) or the E240A mutant of MT1-MMP. Co-expression of caveolin-1 with the wild-type or the ${\Delta}CT$ MT1-MMP decreased the proMMP-2 activation and inhibited collagen degradation and cell migration. Caveolin-1 had no effect on the catalytically inert E240A MT1-MMP. Our findings suggest that caveolin-1 is essential in the down-regulation of MT1-MMP activity by promoting internalization from the cell surface.

A Study on the Anti-wrinkle Activities of Sesamum indicum L. Ethanol Extracts on CCD-986sk (CCD-986sk 세포 내 참깨 에탄올 추출물의 항주름 활성 연구)

  • Joo, Da-Hye;Yoo, Dan-Hee;Lee, Jin-Young
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.42 no.4
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    • pp.377-385
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    • 2016
  • In order to investigate the possibility of Sesamum indicum L. (S. indicum) extract as an active ingredient for wrinkle-care cosmetics, we prepared 70% ethanolic extract of S. indicum and measured its elastase inhibitory activity and collagenase inhibitory activity. We also evaluated the effect of S. indicum extract on protein and mRNA expression of MMPs in fibroblast cell (CCD-986sk). For anti-wrinkle effects, elastase inhibition activities and collagenase inhibition activities were 37.8% and 45% at a dose of $1,000{\mu}g/mL$ of S. indicum 70% ethanol extract. For a cell viability test, measured on fibroblast cell by ethanol extract of S. indicum, results showed 96% with cell viability at $100{\mu}g/mL$ concentration. According to the results of western blot of ethanol extract from S. indicum the expression of the matrix metalloproteinase-1 (MMP-1), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-3 (MMP-3) protein was decreased by 63%, 43%, 49% at $100{\mu}g/mL$ concentration. Reverse transcription-polymerase chain reaction (PCR) of ethanol extract from S. indicum showed that the expression of MMP-1, MMP-2, MMP-3 mRNA was decreased by 82%, 79%, 82% at $100{\mu}g/mL$ concentration. The findings suggest that 70% ethanol extract from S. indicum has potential as a cosmeceutical ingredient with anti-wrinkle effects.

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.

Inhibitory Effect of Gallic Aicd on TNF-α-induced matrix metalloproteinase-1 (MMP-1) in HaCaT Cells (HaCaT세포에서 TNF-α에 의해 유도되는 MMP-1에 대한 Gallic Aicd의 저해 효과)

  • Kim, Pom-Ho
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.14 no.11
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    • pp.5778-5784
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    • 2013
  • In order to develop anti-wrinkle agent, we measured the anti-oxidative activity of gallic acid (GA) from Paeonia suffruticosa Andrews and investigated its cytotoxicity in HaCaT cells and then investigated its effect on tumor necrosis factor alpha (TNF-${\alpha}$)-induced matrix metalloproteinase-1 (MMP-1) mRNA, protein expressions and secretion in same cells. GA showed anti-oxidative activity with $IC_{50}$ of 30 ${\mu}g/mL$ and its activity was higher than that of butylated hydroxyanisol (BHA). GA showed weak cytotoxicity with high concentration (200 ${\mu}g/mL$) in HaCaT cells. MMP-1 mRNA, protein expression and secretion induced by tumor necrosis factor alpha (TNF-${\alpha}$) in HaCaT cells were significantly decreased by treatment of GA with dose-dependent manner(p<0.05). Therefore, our findings suggest that GA can be useful as an active ingredient for cosmeceuticals of anti-wrinkle effects.

Response to Bee Venom Acupuncture and Polymorphism of Matrix Metalloproteinase-1 Gene in Korean Patients with Rheumatoid Arthritis (한국인 류마티스 관절염 환자의 봉독약침 치료반응과 Matrix Metalloproteinase-1의 유전자 다형성 연구)

  • Lee, Sang-hoon;Choi, Do-young;Lee, Yun-ho
    • Journal of Acupuncture Research
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    • v.21 no.1
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    • pp.211-225
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    • 2004
  • 목적 : 류마티스 관절염 환자의 골 파괴에 중요한 역할을 하는 것으로 알려진 Matrix Metalloproteinase-1(MMP-1) 유전자의 단일 염기 다형성을 분석하고, 나아가 봉독약침 치료에 대한 반응과의 연관성을 조사하기 위하여 본 연구를 시행하였다. 방법 : 미국류마티스학회의 류마티스 관절염 기준에 해당하는 122명의 한국인 류마티스 관절염 환자와 건강한 92명의 대조군을 대상으로 pyrosequencing 방법을 이용하여 MMP-1 유전자의 -519 위치의 다형성을 비교 분석하였으며, 류마티스 관절염 환자군을 다시 유전자 유형에 따라 동통 관절수, 종창 관절수, 조기 강직, 통증 강도, 삶의 질 평가도구인 HAQ, 환자 및 의사의 전반적 질병상태 평가, ESR, CRP 등의 항목을 치료 전후 평가하여 비교 분석하였다. 결과 : 1. 류마티스 환자군과 건강한 대조군간에 MMP-1 유전자의 단일 염기 다형성의 유전자형의 분포와 대립유전자 발현 빈도에 통계적으로 유의한 차이가 나타났으며, 이는 MMP-1 유전자 다형성이 한국인 류마티스 관절염 환자의 질병 감수성과 관련이 있음을 추정할 수 있다. 2. 각 유전자형 그룹간 치료전 질병의 중증도 평가에서 임상 평가와 혈액의 급성 염증 반응물질 평가에서 통계적으로 유의한 차이는 없었다. 3. 급성 염증 반응의 지표인 ESR과 CRP level의 봉독약침 치료 전후 변화는 MMP-1의 유전자 다형성과 유의한 연관이 없었다. 4. 각 유전자형 그룹간의 치료 전후 질병 호전도 비교에서, AA 유전자형이 종창 관절수 평가에서 더나은 호전을 보였으며, 다른 모든 평가에서는 통계적으로 유의한 차이가 없었으며, 향후 관련 유전자와의 연관성 연구가 필요하다고 사료된다.

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Essential Role for c-jun N-terminal Kinase on tPA-induced Matrix Metalloproteinase-9 Regulation in Rat Astrocytes

  • Lee, Sun-Ryung
    • Animal cells and systems
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    • v.10 no.2
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    • pp.79-83
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    • 2006
  • Tissue plasminogen activator (tPA) is used to lyse clots and reperfuse brain in ischemic stroke. However, sideeffects of intracerebral hemorrhage (ICH) and edema limit their clinical application. In part, these phenomena has been linked with elevations in matrix metalloproteinase-9 (MMP-9) in neurovascular unit. However little is known about their regulatory signaling pathways in brain cells. Here, I examine the role of MAP kinase pathways in tPA-induced MMP-9 regulation in rat cortical astrocytes. tPA $(1-10\;{\mu}g/ml)$ induced dose-dependent elevations in MMP-9 and MMP-2 in conditioned media. Although tPA increased phosphorylation in two MAP kinases (ERK, JNK), only inhibition of the JNK pathway by the JNK inhibitor SP600126 significantly reduced MMP-9 upregulation. Neither ERK inhibition with U0126 nor p38 inhibition with SB203580 had any significant effects. Taken together, these results suggest that c-jun N-terminal kinase (JNK) plays an essential role for tPA-induced MMP-9 upregulation.

LIGHT is Expressed in Foam Cells and Involved in Destabilization of Atherosclerotic Plaques through Induction of Matrix Metalloproteinase-9 and IL-8

  • Kim, Won-Jung;Lee, Won-Ha
    • IMMUNE NETWORK
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    • v.4 no.2
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    • pp.116-122
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    • 2004
  • Background: LIGHT (TNFSF14) is a member of tumor necrosis factor superfamily and is the ligand for TR2 (TNFRSF14/HVEM). LIGHT is known to have proinflammatory roles in atherosclerosis. Methods: To find out the expression pattern of LIGHT in atherosclerotic plaques, immunohistochemical analysis was performed on human carotid atherosclerotic plaque specimens. LIGHT induced atherogenic events using human monocytic cell line THP-1 were also investigated. Results: Immunohistochemical analysis revealed expression of LIGHT and TR2 in foam cell rich regions in the atherosclerotic plaques. Double immunohistochemical analysis further confirmed the expression of LIGHT in foam cells. Stimulation of THP-1 cells, which express TR2, with either recombinant LIGHT or immobilized anti-TR2 monoclonal antibody induced interleukin-8 and matrix metalloproteinase(MMP)-9. Electrophoretic mobility shift assay demonstrated that LIGHT induces nuclear localization of transcription factor, nuclear factor $(NF)-{\kappa}B$. LIGHT induced activation of MMP-9 is mediated by $NF-{\kappa}B$, since treatment of THP-1 cells with the $NF-{\kappa}B$ inhibitor PDTC (pyrrolidine dithiocarbamate) completely blocked the activation of MMP-9. Conclusion: These data indicate that LIGHT is expressed in foam cells in atherosclerotic plaques and is involved in atherogenesis through activation of pro-atherogenic cytokine IL-8 and destabilization of plaque by inducing matrix degrading enzyme.