• Title/Summary/Keyword: Extracellular

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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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    • 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.

Protection of Polaromonas naphthalenivorans CJ2 from Naphthalene Toxicity by Extracellular Polysaccharide Capsules

  • Park, Min-Jeong;Jeon, Ye-Ji;Madsen, Eugene L.;Jeon, Che-Ok
    • Journal of Applied Biological Chemistry
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    • v.50 no.2
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    • pp.41-45
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    • 2007
  • Polaromonas naphthalenivorans CJ2, responsible for naphthalene degradation at a coal tar contaminated site, was isolated on MSB agar media supplied with naphthalene vapor as the sole carbon source at $10^{\circ}C$. The strain is not isolated under the same isolation condition using the same soil sediment at $20^{\circ}C$ although its optimum temperature is about $20^{\circ}C$. In this work we explored the reason why strain CJ2 could not have been isolated on MSB agar with naphthalene vapor at $20^{\circ}C$. Dispersed CJ2 cells in PBS buffer formed colonies on MSB agar with naphthalene vapor at $10^{\circ}C$ with low naphthalene vapor pressure, but not at $20^{\circ}C$ with high naphthalene vapor pressure. However, streaked cells without resuspension grew on MSB agar with naphthalene vapor at $10^{\circ}C,\;20^{\circ}C$, and even $25^{\circ}C$. Investigation of scanning electron microscopy showed that CJ2 cells formed extracellular polysaccharide (EPS) capsules, which were released easily from CJ2 cells by just dispersion. Therefore, it is concluded that strain CJ2 is able to overcome the naphthalene toxicity by forming a capsule-type barrier around the cells although it is susceptible to naphthalene toxicity at high temperature.

Fluvastatin inhibits advanced glycation end products-induced proliferation, migration, and extracellular matrix accumulation in vascular smooth muscle cells by targeting connective tissue growth factor

  • Hwang, Ae-Rang;Nam, Ju-Ock;Kang, Young Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.2
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    • pp.193-201
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    • 2018
  • Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.

Protective actions of Rubus coreanus ethanol extract on collagenous extracellular matrix in ultraviolet-B irradiation-induced human dermal fibroblasts

  • Bae, Ji-Young;Lim, Soon-Sung;Choi, Jung-Suk;Kang, Young-Hee
    • Nutrition Research and Practice
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    • v.1 no.4
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    • pp.279-284
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    • 2007
  • Solar ultraviolet (UV) irradiation leads to distinct changes in the skin connective tissues by degradation of collagen, which is a major structural component in the extracellular matrix. UV irradiation induces the production of matrix metalloproteinases (MMP) capable of attacking native fibrillar collagen and responsible for inhibiting the construction of collagenous extracellular matrix. In this study, we attempted to investigate the protective actions of Rubus coreanus ethanol extract (RCE) on the MMP production and the consequent procollagen/collagen degradation in UV-B-irradiated human dermal fibroblasts. The analytical data showed that Rubus coreanus ethanol extract was mostly comprised of cyanidin 3-rutinoside. Pre-treatment of fibroblasts with this extract inhibited UV-B-induced production of MMP-1, MMP-8 and MMP-13 in dose-dependent manners. In addition, Western blot analysis and immunocytochemical staining assay revealed that RCE markedly augmented the cellular levels of procollagen/collagen declined in UV-B-exposed dermal fibroblasts. These results demonstrate that RCE blocks UV-B-induced increase of the collagen degradation by inhibiting MMP production. Thus, RCE may act as an agent inhibiting excessive dermal collagen degradation leading to the skin photoaging.

Purification and Characterization of Extracellular Adenosine Deaminase from Streptomyces sp. J-350P (Streptomyces sp. J-350P가 생산하는 세포외 Adenine Deaminase의 부분정제 및 성질)

  • 박정혜;전홍기
    • Microbiology and Biotechnology Letters
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    • v.15 no.5
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    • pp.306-311
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    • 1987
  • After series of purification by means of ammonium sulfate fractionation, the 1st and 2nd DEAE-Cellulose, DEAE-Sephadex A-50, and Sephacryl S-200 superfine gel filtration, the activity of extracellular adenine deaminase from Streptomyces sp. J-350P increased 1764 fold and the yield was 0.3% of original activity. The enzyme was stable at the pH range 6.5 to 8.5 and at up to 5$0^{\circ}C$. The optimum pH and temperature of the enzyme were around 6.5 and 35$^{\circ}C$. The molecular weight ol the enzyme was estimated as 36, 000 by calibrated Sephacryl S-200 superfine column chromatography.

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The Enzymatic Properties of Extracellular Adenine Deaminnse from Streptomyces sp. J-350P (Streptomyces sp. J-350P가 생산하는 세포외 Adenine Deaminase의 효소학적 성질)

  • 전홍기;박정혜;김태숙
    • Microbiology and Biotechnology Letters
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    • v.15 no.5
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    • pp.312-318
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    • 1987
  • The apparent Michaelis constant Km of extracellular adenine deaminase from Streptomyces sp. J-350P was 5.8$\times$10$^{-5}$M. The activation energy or the enzyme was calculated from Arrhenius plots for adenine and the value was 3.13 Kcal/mole. The purine analogues, 6-chloropurine, 2,6-diaminopurine, 6-bromopurine, 4-aminopyrazolo[3,4-d] pyrimidine, 6-iodopurine, and 8-bromoadenine were substrates for the enzyme. 6-Dimethylaminopurine was a competitive inhibitor of the enzyme. The enzyme was inhibited by 0.1mM of Fe$^{3+}$, Ag+, and Hg$^{2+}$ and 1 mM of $\alpha$, $\alpha$'-dipyridyl, Penta-chiorophenol, and p-chloromercuribenzoate.

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Involvement of Extracellular Matrix and Integrin-like Proteins on Conidial Adhesion and Appressorium Differentiation in Magnaporthe oryzae

  • Bae, Cheol-Yong;Kim, Soon-Ok;Choi, Woo-Bong;Lee, Yong-Hwan
    • Journal of Microbiology and Biotechnology
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    • v.17 no.7
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    • pp.1198-1203
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    • 2007
  • Conidial adhesion and appressorium formation of Magnaporthe oryzae on the rice surface are important early events in the infection process. As an initiative step to understand the mechanisms underlying these cellular processes at a biochemical level, the effect of a human fibronectin antibody (HFA) and RGD peptides on conidial adhesion and appressorium formation was evaluated. HFA inhibited conidial adhesion and appressorium formation in a dosage-dependent manner. RGD peptides also inhibited these cellular events. Conidial adhesion and appressorium formation inhibited by RGD peptides were restored by chemicals involved in the cyclic AMP-dependent signaling pathway. These results suggest that extracellular matrix proteins might be involved in conidial adhesion and appressorium formation through integrin-like receptor mediation and modulation of cAMP-dependent signaling in the cells.

Extracellular matrixes and neuroinflammation

  • Jang, Dong Gil;Sim, Hyo Jung;Song, Eun Kyung;Kwon, Taejoon;Park, Tae Joo
    • BMB Reports
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    • v.53 no.10
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    • pp.491-499
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    • 2020
  • The extracellular matrix is a critical component of every human tissue. ECM not only functions as a structural component but also regulates a variety of cellular processes such as cell migration, differentiation, proliferation, and cell death. In addition, current studies suggest that ECM is critical for the pathophysiology of various human diseases. ECM is composed of diverse components including several proteins and polysaccharide chains such as chondroitin sulfate, heparan sulfate, and hyaluronic acid. Each component of ECM exerts its own functions in cellular and pathophysiological processes. One of the interesting recent findings is that ECM is involved in inflammatory responses in various human tissues. In this review, we summarized the known functions of ECM in neuroinflammation after acute injury and chronic inflammatory diseases of the central nerve systems.

Anti-wrinkle effect of bone morphogenetic protein receptor 1a-extracellular domain (BMPR1a-ECD)

  • Yoon, Byung-Hak;Jeon, Yun-Hui;Hwang, Byunghee;Kwon, Hyuknam;Choe, Senyon;Yang, Zungyoon
    • BMB Reports
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    • v.46 no.9
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    • pp.465-470
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    • 2013
  • Bone morphogenetic proteins (BMPs) have diverse and important roles in the proliferation and differentiation of adult stem cells in our tissues. Especially, BMPs are well known to be the main inducers of bone formation, by facilitating both proliferation and differentiation of bone stem cells. Interestingly, in skin stem cells, BMPs repress their proliferation but are indispensable for the proper differentiation into several lineages of skin cells. Here, we tested whether BMP antagonists have an effect on the prevention of wrinkle formation. For this study we used an in vivo wrinkle-induced mouse model. As a positive control, retinoic acid, one of the top anti-wrinkle effectors, showed a 44% improvement compared to the non-treated control. Surprisingly, bone morphogenetic protein receptor 1a extracellular domain (BMPR1a-ECD) exhibited an anti-wrinkle effect which was 6-fold greater than that of retinoic acid. Our results indicate that BMP antagonists will be good targets for skin or hair diseases.

Antioxidant Activity of Manno-oligosaccharides Derived from the Hydrolysis of Polymannan by Extracellular Carbohydrase of Bacillus N3

  • Amna, Kashif Shaheen;Park, So Yeon;Choi, Min;Kim, Sang Yeon;Yoo, Ah Young;Park, Jae Kweon
    • Journal of Marine Bioscience and Biotechnology
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    • v.10 no.1
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    • pp.9-17
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    • 2018
  • The aim of this study is to elucidate the biochemical properties of manno-oligosaccharides (MOS) hydrolyzed by extracellular enzyme of Bacillus N3. We strived to characterize the biochemical properties of MOS since N3 can effectively hydrolyzed natural polymannans such as galactomannan (GM) and konjac (glucomannan, KM), respectively. The hydrolysis of GM and KM was applied by the strain N3 in terms of reducing sugars and the highest production of reducing sugars was estimated to be about 750 mg/L and 370 mg/L respectively, which were quantified after 7 days of cultivation in the presence of both substrates. Hydrolysates derived from the hydrolysis of KM showed the significant antioxidant activity based on DPPH and ABTS radical scavenging activity with increasing of tyrosinase inhibitory activity. On the other hand, hydrolysates derived from the hydrolysis of GM showed only ABTS radical scavenging activity without showing significant changes on tyrosinase inhibitory activity. Our data suggest that those biological characteristics may be depend on the primary structure and the size of MOS, which may be useful as potent additives for diet foods.