• Title/Summary/Keyword: endogenous enzymes

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Roles of Matrix Metalloproteinases in Tumor Metastasis and Angiogenesis

  • Yoon, Sang-Oh;Park, Soo-Jin;Yun, Chang-Hyun;Chung, An-Sik
    • BMB Reports
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    • v.36 no.1
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    • pp.128-137
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    • 2003
  • Matrix metalloproteinases (MMPs), zinc dependent proteolytic enzymes, cleave extracellular matrix (ECM: collagen, laminin, firbronectin, etc) as well as non-matrix substrates (growth factors, cell surface receptors, etc). The deregulation of MMPs is involved in many diseases, such as tumor metastasis, rheumatoid arthritis, and periodontal disease. Metastasis is the major cause of death among cancer patients. In this review, we will focus on the roles of MMPs in tumor metastasis. The process of metastasis involves a cascade of linked, sequential steps that involve multiple host-tumor interactions. Specifically, MMPs are involved in many steps of tumor metastasis. These include tumor invasion, migration, host immune escape, extravasation, angiogenesis, and tumor growth. Therefore, without MMPs, the tumor cell cannot perform successful metastasis. The activities of MMPs are tightly regulated at the gene transcription levels, zymogen activation by proteolysis, and inhibition of active forms by endogenous inhibitors, tissue inhibitor of metalloproteinase (TIMP), and RECK. The detailed regulations of MMPs are described in this review.

Protective Activity of Seolitae Chungkukjang Added with Green Tea against Cellular Oxidative Stress induced by AAPH

  • Park, Hyun-Young;Lee, Hee-Seob;Cho, Eun-Ju
    • Preventive Nutrition and Food Science
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    • v.14 no.1
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    • pp.37-42
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    • 2009
  • The protective activity of seolitae chungkukjang added with green tea against oxidative stress was investigated under the cellular systems using LLC-$PK_1$ cells. The treatment of 2,2'-azobis(2-aminopropane) dihydrochloride (AAPH) showed increase in lipid peroxidation, and decrease in endogenous antioxidant enzymes activity and cell viability. However, the methanol extract of seolitae chungkukjang inhibited lipid peroxidation by 58.3%, and increased cell viability up to more than 60%. In addition, it enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities. Seolitae chungkukjang improved oxidative stress-induced cellular injury through the radical scavenging activities. In particular, the addition of green tea in seolitae chungkukjang showed stronger effect against oxidative stress induced by AAPH. The more addition of green tea resulted in the greater antioxidative effect through elevation in activities of SOD and GSH-Px, and inhibition of lipid peroxidation, eventually leading to increase in cell viability. Theses results suggested that seolitae chungkukjang added with green tea have protective effects from cellular oxidative damage and could be considered as an application for the development of chungkukjang with functionality.

$\alpha$-Phenyl-N-t-butylnitrone Protects Oxidative Damage to HepG2 Cells

  • Kim, Sun-Yee;Kim, Ryung-Hyo;Huh, Tae-Lin;Park, Jeen-Woo
    • BMB Reports
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    • v.34 no.1
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    • pp.43-46
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    • 2001
  • $\alpha$-Phenyl-N-t-butylnitrone (PBN) is one of the most widely used spin-trapping compounds for investigating the existence of free radicals in biological systems. Recently, there has been considerable interest in the antioxidant nature of PBN on degenerative diseases, presumably related to oxidative stress. In the present study, the protective effect of PBN on the HepG2 cell line under oxidative stress was investigated. When the HepG2 cells were exposed to oxidant, such as hydrogen peroxide, menadione, or ethanol, the protective role of PBN was manifested as a reduction in trypan blue uptake and a decrease in the endogenous production of oxidants, as measured by the oxidation of 2',7'-dichlorodihydrofluorescin. The modulation of activity of major antioxidant enzymes, such as superoxide dismutase and catalase, was not significantly different either in the presence or in the absence of PBN. This indicates that PBN acts as a direct scavenger of reactive oxygen species.

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Microbiome-Linked Crosstalk in the Gastrointestinal Exposome towards Host Health and Disease

  • Moon, Yuseok
    • Pediatric Gastroenterology, Hepatology & Nutrition
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    • v.19 no.4
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    • pp.221-228
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    • 2016
  • The gastrointestinal exposome represents the integration of all xenobiotic components and host-derived endogenous components affecting the host health, disease progression and ultimately clinical outcomes during the lifespan. The human gut microbiome as a dynamic exposome of commensalism continuously interacts with other exogenous exposome as well as host sentineling components including the immune and neuroendocrine circuit. The composition and diversity of the microbiome are established on the basis of the luminal environment (physical, chemical and biological exposome) and host surveillance at each part of the gastrointestinal lining. Whereas the chemical exposome derived from nutrients and other xenobiotics can influence the dynamics of microbiome community (the stability, diversity, or resilience), the microbiomes reciprocally alter the bioavailability and activities of the chemical exposome in the mucosa. In particular, xenobiotic metabolites by the gut microbial enzymes can be either beneficial or detrimental to the host health although xenobiotics can alter the composition and diversity of the gut microbiome. The integration of the mucosal crosstalk in the exposome determines the fate of microbiome community and host response to the etiologic factors of disease. Therefore, the network between microbiome and other mucosal exposome would provide new insights into the clinical intervention against the mucosal or systemic disorders via regulation of the gut-associated immunological, metabolic, or neuroendocrine system.

The GSTP1 Ile105Val Polymorphism is not Associated with Susceptibility to Colorectal Cancer

  • Khabaz, Mohamad Nidal
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.6
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    • pp.2949-2953
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    • 2012
  • The glutathione S transferase (GST) family is a major part of cellular defense mechanisms against endogenous and exogenous substances, many of which have carcinogenic potential. Alteration in the expression level or structure of the glutathione-S-transferase (GST) enzymes may lead to inadequate detoxification of potential carcinogens and consequently contribute to cancer development. A member of the glutathione-S-transferase (GST) family, GSTP1, is an attractive candidate for involvement in susceptibility to carcinogen-associated colorectal cancer. An $Ag{\rightarrow}G$ transition in exon 5 resulting in an Ile105Val amino acid substitution has been identified which alters catalytic efficiency. The present study investigated the possible impact of Ile105Val GSTP1 polymorphism on susceptibility to colorectal cancer. in Jordan We examined 90 tissue samples previously diagnosed with colorectal carcinoma, and 56 non-cancerous colon tissues. DNA was extracted from paraffin embedded tissues and the status of the GSTP1 polymorphism was determined using a polymerase chain reaction restriction fragment length polymorphism (RFLP) method. No statistically significant differences were found between colorectal cancer cases and controls for the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes. The glutathione S-transferase polymorphism was not associated with risk in colorectal cancer cases in Jordan stratified by age, sex, site, grade or tumor stage. In conclusion, the GSTP1 Ile105Val polymorphism is unlikely to affect the risk of colorectal cancer.

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

  • Schutz, R.;Imfeld, D.
    • Proceedings of the SCSK Conference
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    • 2003.09a
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    • pp.590-600
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    • 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.

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Effect of Salicylic Acid on Growth and Chilling Tolerance of Cucumber Seedlings

  • Lee, Gui-Soon;Hong, Jung-Hee
    • Journal of Environmental Science International
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    • v.11 no.11
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    • pp.1173-1181
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    • 2002
  • The present study was undertaken to investigate the effect of low temperature and salicylic acid(SA) on the chilling tolerance of acclimated and nonacclimated cucumber(Cucurmis sativus L.) seedlings. The acclimation phenomenon was characterized in chilling-sensitive cucumber seedlings and found to have a significant effect on the survival and shoot dry weights. The injuries experienced by the acclimated seedlings in the third leaf stage were on average smaller by half than those experienced by the nonacclimated seedlings. Chilling also caused a large increase in the free proline levels, regardless of the acclimation status. Exogenous treatment with SA(0.5mM) resulted in improved growth and survival of the nonacclimated chilled seedlings, indicating that SA induced chilling tolerance and SA and acclimation had common effects. The application of cycloheximide in the presence of SA restored the acclimation-induced chilling tolerance. The elevated proline level observed in the cold-treated and SA-treated plants was more pronounced in the light than in the dark at a chilled temperature, indicating that endogenous proline may play a role in chilling tolerance by stabilizing the water status in response to chilling. From these results it is suggested that SA provided protection against low-temperature stress by increasing the proline accumulation, and pre-treatment with SA may induce antioxidant enzymes leading to increased chilling tolerance.

The effect of lead on matrix metalloproteinase-9 expression in rat primary glial cells

  • Park, Min-Sik;Lee, Woo-Jong;Kim, Young-Eun;Ko, Kwang-Ho
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.84-84
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    • 2003
  • Lead has long been considered as a toxic environmental pollutant, which severely damages central nervous system. Lead can cause hypo- and de-myelination, and glial cells are closely related with myelination or demyelination. Matrix metalloproteinases (MMPs) are proteolytic enzymes that are involved in the remodelling of the extracellular matrix in a variety of physiological and pathological processes. MMPs also seem to be important in the pathogenesis of inflammatory demyelinating diseases of the central and peripheral nervous system. In this study, we investigated whether lead affects MMP-9 expression in rat primary glial cells. Treatment of 0.1-5 ${\mu}$M lead dose- and time-dependently increased MMP-9 expression in rat primary glial cells. The activity of MMPs was determined using zymography. Lead activated Erk(1/2) but neither of the other endogenous MAP kinases, p38 or JNK. Inhibition of Erk(1/2) activation by PD98059, a MEK inihibitor, prevented lead-induced expression of MMP-9. The results of the present study suggest that lead intoxication may adversely affect brain function at least in part by inducing MMP-9 expression through Erk(1/2) activation in primary glial cells.

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Gene Expression of Taurine Transporter and Taurine Biosynthetic Enzyme During Embryonic Development

  • Yoon, Seyng-Hyun;Kim, Ha-Won
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.87-87
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    • 2003
  • Taurine (2-aminoethanesulfonic acid, $^{+}NH_3CH_2CH_2{SO_3}^{-}$) is endogenous $\beta$-amino acid which is essential in fetal nutrition and development and is present in abundant quantities in several tissues of fetus. In utero, taurine deficiency causes abnormal development and abnormal function of brain, retina, kidney and myocardium. Thus, transfer of taurine into fetus is important during embryonic development. Taurine transporter (TauT) has 12 hydrophobic membrane -spanning domains, which is typical of the $Na^{+}$- and $Cl^{-}$-dependent transporter gene family. Among the various biosynthetic enzymes of taurine, cysteine sulfinic acid decarboxylase (CSD) is the rate-limiting enzyme for biosynthesis of taurine. However, the enzyme activities of taurine biosynthesis are limited in early stage of embryonic development. To analyze the expression period of TauT and CSD during embryonic development, we have investigated the gene expression of TauT and CSD using reverse transcriptase polymerase chain reaction (RT-PCR) in mouse and chicken embryos. RT-PCR anaylsis revealed that both TauT and CSD mRNAs were already expressed at Day-4.5 in mouse embryo. In chicken whole embryo, TauT and CSD mRNAs began to appear on developing times of 48 hrs and 12 hrs, respectively. TauT mRNA was detected in the organs of heart, brain and eye of the day-3 chicken embryo. Our data show that TauT and CSD mRNAs were expressed in early stage of embryonic development.

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Changes in Cathepsin Activity during Low-Temperature Storage and Sous Vide Processing of Beef Brisket

  • Kaur, Lovedeep;Hui, Seah Xin;Boland, Mike
    • Food Science of Animal Resources
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    • v.40 no.3
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    • pp.415-425
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    • 2020
  • It is believed that two main proteolytic systems are involved in the tenderization of meat: the cathepsins and the calpains. Many researchers consider the calpain system to be the major contributor to meat tenderness during post-mortem storage. However, the role and activity of cathepsins during post-mortem storage or low temperature meat processing is unclear, particularly for the tough meat cuts like brisket. Thus, the study was designed to investigate the effects of cold (refrigerated and frozen) storage and sous vide processing on the activities of cathepsin B, H, and L in beef brisket. There were no significant changes in pH and cathepsin H activity throughout the 18 d of storage at both temperatures. However, an increase in cathepsin B activity was observed during the first 4 d at both storage temperatures, but subsequently the activity remained unchanged. Cathepsins B and L were found to be more heat stable at sous vide temperatures (50℃ for 24 h, 55℃ for 5 h and at 60℃ and 70℃ for 1 h) compared to cathepsin H. Cathepsin B+L activity was found to increase after sous vide cooking at 50℃ for 1 h but decreased to about 47% relative to the uncooked control after 24 h of cooking. These results suggest that cathepsins B and L may contribute to the improved meat tenderness usually seen in sous vide cooked brisket meat.