• 제목/요약/키워드: MMPs

검색결과 370건 처리시간 0.022초

Matrix Metalloproteinases, New Insights into the Understanding of Neurodegenerative Disorders

  • Kim, Yoon-Seong;Joh, Tong-H.
    • Biomolecules & Therapeutics
    • /
    • 제20권2호
    • /
    • pp.133-143
    • /
    • 2012
  • Matrix metalloproteinases (MMPs) are a subfamily of zinc-dependent proteases that are re-sponsible for degradation and remodeling of extracellular matrix proteins. The activity of MMPs is tightly regulated at several levels including cleavage of prodomain, allosteric activation, com-partmentalization and complex formation with tissue inhibitor of metalloproteinases (TIMPs). In the central nervous system (CNS), MMPs play a wide variety of roles ranging from brain devel-opment, synaptic plasticity and repair after injury to the pathogenesis of various brain disorders. Following general discussion on the domain structure and the regulation of activity of MMPs, we emphasize their implication in various brain disorder conditions such as Alzheimer's disease, multiple sclerosis, ischemia/reperfusion and Parkinson's disease. We further highlight accumu-lating evidence that MMPs might be the culprit in Parkinson's disease (PD). Among them, MMP-3 appears to be involved in a range of pathogenesis processes in PD including neuroinflamma-tion, apoptosis and degradation of ${\alpha}$-synuclein and DJ-1. MMP inhibitors could represent poten-tial novel therapeutic strategies for treatments of neurodegenerative diseases.

Morphological remodeling in mouse vagina due to hormonal hypersecretion

  • Oh, Min-Gee;Kim, Sang-Hwan
    • 한국동물생명공학회지
    • /
    • 제37권1호
    • /
    • pp.42-47
    • /
    • 2022
  • This study aimed to determine whether hormonal hypersecretion could cause morphological problems in the mouse vagina and affect the ovaries and nearby extra uterine organs. All mice were synchronized to estrus before the experiment. Then human chorionic gonadotropin (hCG), progesterone, and testosterone were continuously administered for about 6 days to maintain hormone hypersecretion, and then morphological changes were analyzed, and Matrix metalloproteinases (MMPs) activity and Casp-3 expression were evaluated. As a result of the analysis, in the case of hCG, the morphological change did not show a significant difference from the vagina of normal estrus. In the case of progesterone, changes were observed in the mucosa zone and basal membrane, and it was confirmed that the activity of MMPs was increased in squamous epithelium cells. On the other hand, in the case of testosterone, overall changes in vaginal tissues were observed, and MMPs activity was increased to a very high level in all sections. The expression of Casp-3 was also the highest compared to other groups. Therefore, as a result of this study, it is thought that hormone hypersecretion affects the morphological changes of the vagina other than the ovaries and uterus and induces the activity of MMPs to cause morphological degeneration of tissues.

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
    • /
    • 제37권1호
    • /
    • pp.2-8
    • /
    • 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.

Stability and vibration behavior of cellular plates with different cell arrays using a numerical approach

  • Chuan-Xiong Li
    • Structural Engineering and Mechanics
    • /
    • 제85권6호
    • /
    • pp.709-716
    • /
    • 2023
  • In this paper, the shape factors of cellular meta-material plates (MMPs) having diverse cell arrays have been determined as the first attempt to finally examine their stability and vibrational frequencies. The MMPs are actually constructed from cylindrical or cubic cellular cores and two face sheets. Sandwich-like MMPs with circular and square holes in the face sheets have been selected in such a way that the effective material properties depend on the cellular architectures. For verifying the frequency results, finite element (FE) simulations are done in Abaqus software. Several graphical results have been represented to explore the effects of cellular architectures on vibrational frequencies and dynamic responses of the MMPs. Also, the deflection-frequency and stability curves in the case of forced vibrations have been plotted for diverse cell arrays.

미니돼지 정자 동결 보존에 Tea-N-Tris의 첨가가 체외 수정 및 MMPs 활성에 미치는 영향 (Impact of In-vitro Fertility and Matrix Metalloproteinases Activation of Spermatozoa by Supplement of Tea-N-Tris to Sperm Cryopreservation of Miniature Pig)

  • 김상환;강현아;박용수;윤종택
    • 한국수정란이식학회지
    • /
    • 제29권1호
    • /
    • pp.83-90
    • /
    • 2014
  • The main purpose of this study is to estimate the effect of adding Tea-N-Tris (TES) to the freezing buffer for miniature pig sperm. In particular, we attempted to identify the association between the MMPs expression and the fertility and viability of frozen sperm from each extender (LEY (Lactose Egg-Yolk), TLE (TES + LEY), TFGE (TES + Fructose + Glucose Egg-Yolk)). In accordance with this, Hypoosmotic Swelling Test (HOST) respond test was the lowest among sperms frozen in LEY while the highest HOST respond was observed among sperms frozen in TLE. Furthermore, we observed MMPs expression in all sperm groups, with pro-MMP showing lower expression than active MMPs. The expression of MMP-9 and MMP-2 was the highest in sperms frozen in LEY, Meanwhile, sperms from the TFGE and TLE group showed lower level of MMP-9 and MMP-2 expression in the order of TLE being the lowest. LEY group showed lower rate of blastocyst development than the TES supplement group, although the difference was not statistically significant. Meanwhile the rate of blastocyst development appeared similar when sperms from TLE and TFGE group were used for IVF. Together, these results indicate that adding Tea-N-Tris to the sperm freezing buffer only suppresses MMPs protein activation but also maximize in-vitro fertility, providing a means to improve the success rate in the in vitro manipulation of miniature pig sperm.

헛개나무내의 Matrix Metalloproteinase-9 활성 억제제에 관한 연구 (A study of matrix metalloproteinase-9 inhibitor in Hovenia dulcis Thunberg)

  • 김은호;이광수
    • 분석과학
    • /
    • 제24권2호
    • /
    • pp.135-141
    • /
    • 2011
  • 세포외 기질의 주요 단백질 구성요소들을 가수분해시켜 재편성(turnover)과 재형성(remodeling)에 핵심 역할을 하는 효소가 matrix metalloproteinases (MMPs)이다. MMPs 중에서 MMP-2와 MMP-9는 catalytic domain이 fibronectin-like domain에 의해 hemopexin-like domain 부위와 떨어져 있는 점이 다른 MMP들과 다르다. MMP-9 억제제의 개발로 간암전이를 막을 수 있다고 보고되고 있다. Hovenia dulcis Thunberg에서 MMP-9의 활성을 저해하는 물질을 분리 정제하였고, 분리된 물질에 대한 MMP-9의 활성억제 여부를 확인하였다. Ethyl acetate (EA)에 의해 용출 분리된 두개의 화합물(화합물 A, 화합물 B)과 MeOH로 용출 분리된 한 개의 화합물(화합물 C)에서 MMP-9의 활성에 저해를 보였고, $^1H$$^{13}C$ NMR, GC-MS 그리고 IR로 이들의 구조를 분석하였다. 화합물 A는 hydroxyl기와 methoxyl기로 치환된 벤젠고리를 함유하는 화합물로 catechine 계열로 추정되었으며, 화합물 B와 C는 hydroxyl기와 methoxyl기로 치환된 벤젠 고리와 분자내 carbonyl기를 갖고 있는 nobiletin 계열의 화합물로 추정되었다. 그리고 화합물 A는 MMP-9 활성을 1.0%농도에서 76% 억제하였으며, 화합물 B는 동일한 농도에서 66% 억제하는 것으로 나타났다. 그리고 화합물 C는 1.0%농도에서 71% 억제하는 것으로 나타나 화합물 A가 MMP-9의 활성 저해능이 가장 좋은 것으로 나타났다.

Effect of N-Acetylcysteine on the Matrix Metalloproteinases and Their Inhibitors in Carbon Tetrachloride-Induced Hepatotoxicity

  • N, Kamalakkannan;Al-Numair, Khalid S.;Al-Assaf, Abdullah H.;Al-Shatwi, Ali A.;Vp, Menon
    • Preventive Nutrition and Food Science
    • /
    • 제14권1호
    • /
    • pp.14-20
    • /
    • 2009
  • Matrix metalloproteinases (MMPs) are a group of zinc proteases that serve the function of breaking down extracellular matrix (ECM). The present study evaluated the role of N-acetylcysteine (NAC) on the increased deposition of ECM in hepatic and glomerular fibrosis caused by carbon tetrachloride ($CCl_4$). The activity of MMPs increased and the levels of tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1 and TIMP-2) decreased in the liver and kidney of $CCl_4$-treated rats. Rats treated with $CCl_4$ and NAC showed increased activities of MMPs and decreased levels of TIMP-1 and TIMP-2 in the liver and kidney. Treatment with NAC resulted in the effective degradation of ECM due to an increase in the activities of MMPs and a decrease in the levels of TIMPs.

PRODUCTION OF HUMAN PROTEIN TIMP-2: A HIGHLY EFFECTIVE ANTI-AGING INGREDIENT

  • Schutz, R.;Imfeld, D.
    • 대한화장품학회:학술대회논문집
    • /
    • 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
    • /
    • pp.590-600
    • /
    • 2003
  • The matrix metalloproteinases (MMPs) are a family of enzymes responsible for degrading connective tissue. MMPs catalyze the breakdown of collagen from the extracellular matrix, leading to wrinkle formation and accelerated skin aging. Furthermore, ultraviolet irradiation causes increased expression of certain MMPs. In the extracellular matrix turnover, MMPs are interacting with endogenous regulators named tissue inhibitors of metalloproteinases (TIMPs). Using peptide substrate assays, it has been demonstrated that TIMP-MMP complexes interact highly specifically with $K_{i}$ values of 10$^{-9}$ -10$^{-16}$ M. Therefore applications for TIMP as inhibitor of collagen degradation are suggested for cosmetic anti-aging products to prevent wrinkle formation and loss of elasticity. To date four TIMP proteins (TIMP-1, TIMP-2, TIMP-3 and TIMP-4) have been identified which show a high degree in sequence similarity. The production of human TIMP-2, a 194-residue nonglycosylated protein, was performed by fed-batch culture of Escherichia coli. TIMP-2 accumulated in the bacterial cells in an insoluble form as inclusion bodies. The inclusion bodies were solubilized and the protein refolded to yield the native TIMP-2 in the active form. The integrity of the protein was confirmed by mass analysis, Edman sequencing and gel shift experiments with authentic samples. The inhibitory activity of the refolded and purified TIMP-2 was demonstrated with MMP-1 and MMP-2 assays using synthetic fluorogenic peptide substrates.s.

  • PDF

Curcumin Effect on MMPs and TIMPs Genes in a Breast Cancer Cell Line

  • Hassan, Zeinab Korany;Daghestani, Maha Hassan
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제13권7호
    • /
    • pp.3259-3264
    • /
    • 2012
  • Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix metalloproteinases (MMPs) play an important role in remodeling the extracellular matrix and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of great significance. In this study, the effect of CM is investigated on metastatic MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a mixture of DMEM and Ham's F12 medium and treated with different concentrations of CM (10, 20 and $40{\mu}M$ for various lengths of time. Reverse transcription followed by quantitative real time PCR was used to detect the gene expression levels of MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a concentration- and time-dependent manner. These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells.

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
    • /
    • 제43권1호
    • /
    • pp.62-68
    • /
    • 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.