• Title/Summary/Keyword: endogenous enzymes

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Transcriptional Regulation of the AP-1 and Nrf2 Target Gene Sulfiredoxin

  • Soriano, Francesc X.;Baxter, Paul;Murray, Lyndsay M.;Sporn, Michael B.;Gillingwater, Thomas H.;Hardingham, Giles E.
    • Molecules and Cells
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    • v.27 no.3
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    • pp.279-282
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    • 2009
  • "Two-cysteine" peroxiredoxins are antioxidant enzymes that exert a cytoprotective effect in many models of oxidative stress. However, under highly oxidizing conditions they can be inactivated through hyperoxidation of their peroxidatic active site cysteine residue. Sulfiredoxin can reverse this hyperoxidation, thus reactivating peroxiredoxins. Here we review recent investigations that have shed further light on sulfiredoxin's role and regulation. Studies have revealed sulfiredoxin to be a dynamically regulated gene whose transcription is induced by a variety of signals and stimuli. Sulfiredoxin expression is regulated by the transcription factor AP-1, which mediates its up-regulation by synaptic activity in neurons, resulting in protection against oxidative stress. Furthermore, sulfiredoxin has been identified as a new member of the family of genes regulated by Nuclear factor erythroid 2-related factor (Nrf2) via a conserved cis-acting antioxidant response element (ARE). As such, sulfiredoxin is likely to contribute to the net antioxidative effect of small molecule activators of Nrf2. As discussed here, the proximal AP-1 site of the sulfiredoxin promoter is embedded within the ARE, as is common with Nrf2 target genes. Other recent studies have shown that sulfiredoxin induction via Nrf2 may form an important part of the protective response to oxidative stress in the lung, preventing peroxiredoxin hyperoxidation and, in certain cases, subsequent degradation. We illustrate here that sulfiredoxin can be rapidly induced in vivo by administration of CDDO-TFEA, a synthetic triterpenoid inducer of endogenous Nrf2, which may offer a way of reversing peroxiredoxin hyperoxidation in vivo following chronic or acute oxidative stress.

Anti-oxidative and Anti-inflammatory Effects of Protulaca Oleracea on the LPS-stimulated AGS Cells

  • Kim, Chae-Hyun;Park, Pyeong-Beom;Choe, Seung-Ryeol;Kim, Tae-Heon;Jeong, Jong-Kil;Lee, Kwang-Gyu;Lee, Chang-Hyun;Jeong, Han-Sol
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.23 no.2
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    • pp.488-493
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    • 2009
  • Protulaca oleracea, a widely distributed weed, has been reported to exhibit different health promoting effects. The objective of this study was to evaluate the anti-oxidative and anti-inflammatory effects of P. oleracea on LPS-stimulated AGS cells. The cytotoxicity of P. oleracea in AGS cells was examined by MTT assay. The anti-oxidative effects of P. oleracea were examined by DPPH assay. RT-PCR was carried out to examine the effect of P. oleracea in the mRNA expression of different inflammatory mediators. MTT assay revealed that P. oleracea have almost no cytotoxity in AGS cells. DPPH radical scavenging activities were better than butylated hydroxyl toluene (BHT). The mRNA expression of different endogenous anti-oxidative enzymes (SOD2, GPx3 and catalase) were preserved by P. oleracea in AGS cells. The nitric oxide production and expression of iNOS in LPS stimulated RAW264.7 were suppressed in P. oleracea treated groups. Based on these findings, P. oleracea has protective anti-oxidant and anti-inflammatory effects.

Insect Ornithine Decarboxylase (ODC) Complements SPE1 Knock-Out of Yeast Saccharomyces cerevisiae

  • Choi, Soon-Yong;Park, Hee Yun;Paek, Aron;Kim, Gil Seob;Jeong, Seong Eun
    • Molecules and Cells
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    • v.28 no.6
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    • pp.575-581
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    • 2009
  • Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the biosynthesis of polyamines, which are essential for cell growth, differentiation, and proliferation. This report presents the characterization of an ODC-encoding cDNA (SlitODC) isolated from a moth species, the tobacco cutworm, Spodoptera litura (Lepidoptera); its expression in a polyamine-deficient strain of yeast, S. cerevisiae; and the recovery in polyamine levels and proliferation rate with the introduction of the insect enzyme. SlitODC encodes 448 amino acid residues, 4 amino acids longer than B. mori ODC that has 71% identity, and has a longer C-terminus, consistent with B. mori ODC, than the reported dipteran enzymes. The null mutant yeast strain in the ODC gene, SPE1, showed remarkably depleted polyamine levels; in putrescine, spermidine, and spermine, the levels were > 7, > 1, and > 4%, respectively, of the levels in the wild-type strain. This consequently caused a significant arrest in cell proliferation of > 4% of the wild-type strain in polyamine-free media. The transformed strain, with the substituted SlitODC for the deleted endogenous ODC, grew and proliferated rapidly at even a higher rate than the wild-type strain. Furthermore, its polyamine content was significantly higher than even that in the wild-type strain as well as the spe1-null mutant, particularly with a very continuously enhanced putrescine level, reflecting no inhibition mechanism operating in the putrescine synthesis step by any corresponding insect ODC antizymes to SlitODC in this yeast system.

Identification of Soluble Epoxide Hydrolase Inhibitors from the Seeds of Passiflora edulis Cultivated in Vietnam

  • Cuong, To Dao;Anh, Hoang Thi Ngoc;Huong, Tran Thu;Khanh, Pham Ngoc;Ha, Vu Thi;Hung, Tran Manh;Kim, Young Ho;Cuong, Nguyen Manh
    • Natural Product Sciences
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    • v.25 no.4
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    • pp.348-353
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    • 2019
  • Soluble epoxide hydrolases (sEH) are enzymes present in all living organisms, metabolize epoxy fatty acids to 1,2-diols. sEH in the metabolism of polyunsaturated fatty acids plays a key role in inflammation. In addition, the endogenous lipid mediators in cardiovascular disease are also broken down to diols by the action of sEH that enhanced cardiovascular protection. In this study, sEH inhibitory guided fractionation led to the isolation of five phenolic compounds trans-resveratrol (1), trans-piceatannol (2), sulfuretin (3), (+)-balanophonin (4), and cassigarol E (5) from the ethanol extract of the seeds of Passiflora edulis Sims cultivated in Vietnam. The chemical structures of isolated compounds were determined by the interpretation of NMR spectral data, mass spectra, and comparison with data from the literature. The soluble epoxide hydrolase (sEH) inhibitory activity of isolated compounds was evaluated. Among them, trans-piceatannol (2) showed the most potent inhibitory activity on sEH with an IC50 value of 3.4 μM. This study marks the first time that sulfuretin (3) was isolated from Passiflora edulis as well as (+)-balanophonin (4), and cassigarol E (5) were isolated from Passiflora genus.

Role of PET in Gene Therapy (유전자 치료에서 PET의 역할)

  • Lee, Kyung-Han
    • The Korean Journal of Nuclear Medicine
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    • v.36 no.1
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    • pp.74-79
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    • 2002
  • In addition to the well-established use of positron emission tomography (PET) in clinical oncology, novel roles for PET are rapidly emerging in the field of gene therapy. Methods for controlled gene delivery to living bodies, made available through advances in molecular biology, are currently being employed in animals for research purposes and in humans to treat diseases such as cancer. Although gene therapy is still in its early developmental stage, it is perceived that many serious illnesses could be treated successfully by the use of therapeutic gene delivery. A major challenge for the widespread use of human gene therapy is to achieve a controlled and effective delivery of foreign genes to target cells and subsequently, adequate levels of expression. As such, the availability of noninvasive imaging methods to accurately assess the location, duration, and level of transgene expression is critical for optimizing gene therapy strategies. Current endeavors to achieve this goal include methods that utilize magnetic resonance imaging, optical imaging, and nuclear imaging techniques. As for PET, reporter systems that utilize genes encoding enzymes that accumulate positron labeled substrates and those transcribing surface receptors that bind specific positron labeled ligands have been successfully developed. More recent advances in this area include improved reporter gene constructs and radiotracers, introduction of potential strategies to monitor endogenous gene expression, and human pilot studies evaluating the distribution and safety of reporter PET tracers. The remarkably rapid progress occurring in gene imaging technology indicates its importance and wide range of application. As such, gene imaging is likely to become a major and exciting new area for future application of PET technology.

The Preventive Inhibition of Chondroitin Sulfate Against the $CCl_4$-Induced Oxidative Stress of Subcellular Level

  • Lee, Jin-Young;Lee, Sang-Hun;Kim, Hee-Jin;Ha, Jong-Myung;Lee, Sang-Hyun;Lee, Jae-Hwa;Ha, Bae-Jin
    • Archives of Pharmacal Research
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    • v.27 no.3
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    • pp.340-345
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    • 2004
  • Our work in this study was made in the microsomal fraction to evaluate the lipid peroxidation by measuring superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and malondialdehyde (MDA) and to elucidate the preventive role of CS in the $CCl_4$-induced oxidative stress. The excessive lipid peroxidation by free radicals derived from $CCl_4$ leads to the condition of oxidative stress which results in the accumulation of MDA. MDA is one of the end-products in the lipid peroxidation process and oxidative stress. MDA, lipid peroxide, produced in this oxidative stress causes various diseases related to aging and hepatotoxicity, etc. Normal cells have a number of enzymatic and nonenzymatic endogenous defense systems to protect themselves from reactive species. The enzymes in the defense systems, for example, are SOD, CAT, and GPx. They quickly eliminate reactive oxygen species (ROS) such as superoxide anion free radicalㆍO$^{[-10]}$ $_2$, hydrogen peroxide $H_2O$$_2$ and hydroxyl free radicalㆍOH. CS inhibited the accumulation of MDA and the deactivation of SOD, CAT and GPx in the dose-dependent and preventive manner. Our study suggests that CS might be a potential scavenger of free radicals in the oxidative stress originated from the lipid peroxidation of the liver cells of $CCl_4$-treated rats.

Serine Proteases of Parasitic Helminths

  • Yang, Yong;Wen, Yun jun;Cai, Ya Nan;Vallee, Isabelle;Boireau, Pascal;Liu, Ming Yuan;Cheng, Shi Peng
    • Parasites, Hosts and Diseases
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    • v.53 no.1
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    • pp.1-11
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    • 2015
  • Serine proteases form one of the most important families of enzymes and perform significant functions in a broad range of biological processes, such as intra- and extracellular protein metabolism, digestion, blood coagulation, regulation of development, and fertilization. A number of serine proteases have been identified in parasitic helminths that have putative roles in parasite development and nutrition, host tissues and cell invasion, anticoagulation, and immune evasion. In this review, we described the serine proteases that have been identified in parasitic helminths, including nematodes (Trichinella spiralis, T. pseudospiralis, Trichuris muris, Anisakis simplex, Ascaris suum, Onchocerca volvulus, O. lienalis, Brugia malayi, Ancylostoma caninum, and Steinernema carpocapsae), cestodes (Spirometra mansoni, Echinococcus granulosus, and Schistocephalus solidus), and trematodes (Fasciola hepatica, F. gigantica, and Schistosoma mansoni). Moreover, the possible biological functions of these serine proteases in the endogenous biological phenomena of these parasites and in the host-parasite interaction were also discussed.

Testicular Expression of Steroidogenic Enzyme Genes Is Related to a Transient Increase in Serum 19-nortestosterone during Neonatal Development in Pigs

  • Choi, Nag-Jin;Hyun, Jin Hee;Choi, Jae Min;Lee, Eun Ju;Cho, Kyung Hyun;Kim, Yunje;Chang, Jongsoo;Chung, Il Byung;Chung, Chung Soo;Choi, Inho
    • Asian-Australasian Journal of Animal Sciences
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    • v.20 no.12
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    • pp.1832-1842
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    • 2007
  • Cytochrome P450 aromatase is responsible for the biosynthesis of estrogen. It is also responsible for the endogenous production of 19-nortestosterone (nandrolone), an anabolic androgen unique to pigs. Plasma concentrations of 19-nortestosterone are highest between two and four weeks after birth in male pigs. In the present study, the physiology of 19-nortestosterone was investigated by measuring the mRNA levels of steroidogenic enzymes, estrogen receptors and androgen receptor in the tissues of growing pigs. The expression of aromatase, 17${\alpha}$-hydroxylase and 3${\beta}$-hydroxysteroid dehydrogenase in the testes of male piglets increased between birth and two weeks of age, and then decreased progressively. Similar developmental expressional patterns were observed for 17${\alpha}$-hydroxylase and 3${\beta}$-hydroxysteroid dehydrogenase in the ovaries of female piglets, but without significant aromatase expression. The major form of aromatase expressed in the testes of piglets was identified as type I. Expression of estrogen receptor-${\alpha}$ and -${\beta}$and androgen receptor genes was also detected in both testes and ovaries. A transient elevation of androgen receptor mRNA in male piglets at two weeks of age was also observed in testes. Significant expression of the androgen receptor gene, but not of estrogen receptor-${\alpha}$ and -${\beta}$ genes, was also demonstrated in adipose tissue and muscle. We conclude that the observed increase in the testicular expression of aromatase in male pigs could account for the production of large amounts of 19-nortestosterone at between two and four weeks of age in males. Androgen receptor and 19-nortestosterone appeared to be important for testicular development and might contribute to sexual dimorphism in body composition and muscle development in juvenile pigs.

Treatments Effect on Biological Values of Defatted Rice Polishings

  • Khalique, Anjum;Lone, K.P.;Khan, A.D.;Pasha, T.N.
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.2
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    • pp.209-216
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    • 2006
  • Defatted rice polishings (DRP) was subjected to chemical treatments i.e., 0.4 N HCl, and 6% $H_2O_2$, with or without physical treatment i.e. extrusion cooking. The treated DRP was evaluated chemically and biologically using male broiler chicks (108) of approximately uniform weight, selected out of 220 chicks, previously fed on commercial diets for 7 days as a settlement period. The chicks were then divided into 36 experimental units of 3 chicks each. Each experimental diet was randomly allotted to three experimental units and fed for 10 days to broiler chicks. The experimental diets were designated as A (Commercial), B (10% HCl treated DRP), C (20% HCl treated DRP), D (10% HCl plus extruded DRP), E (20% HCl plus extruded DRP), F (10% $H_2O_2$ DRP) and G (20% $H_2O_2$ DRP), H (10% $H_2O_2$ plus extrusion DRP) and I (20% $H_2O_2$ plus extrusion DRP), J (10% untreated DRP), K (20% untreated DRP) and L (Protein free). The birds fed on diet L were used to measure the endogenous nitrogen loss. The biological evaluations of diets containing differently treated DRP were compared with a commercial feed and feeds containing untreated defatted rice polishings. It was observed that these treatments liberated bound nutrients, making them more accessible to the normal digestive enzymes and increased their apparent nutrient availability. This process probably also detoxified the anti-nutritive factors i.e. phytates, lectin, trypsin inhibitor present in DRP. The results of the feeding trials revealed that diets containing 6% $H_2O_2$ treated DRP showed better weight gain, feed consumption and utilization, protein efficiency and digestibility, biological value and net protein utilization than all other treatments.

Targeting Nrf2-Mediated Gene Transcription by Triterpenoids and Their Derivatives

  • Loboda, Agnieszka;Rojczyk-Golebiewska, Ewa;Bednarczyk-Cwynar, Barbara;Zaprutko, Lucjusz;Jozkowicz, Alicja;Dulak, Jozef
    • Biomolecules & Therapeutics
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    • v.20 no.6
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    • pp.499-505
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    • 2012
  • Chemoprevention represents a strategy designed to protect cells or tissues against various carcinogens and carcinogenic metabolites derived from exogenous or endogenous sources. Recent studies indicate that plant-derived triterpenoids, like oleanolic acid, may exert cytoprotective functions via regulation of the activity of different transcription factors. The chemopreventive effects may be mediated through induction of the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor. Activation of Nrf2 by triterpenoids induces the expression of phase 2 detoxifying and antioxidant enzymes such as NAD(P)H quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) - proteins which can protect cells or tissues against various toxic metabolites. On the other hand, inhibition of other transcription factors, like NF-${\kappa}B$ leads to the decrease in the pro-inflammatory gene expression. Moreover, the modulation of microRNAs activity may constitute a new mechanism responsible for valuable effects of triterpenoids. Recently, based on the structure of naturally occurring triterpenoids and with involvement of bioinformatics and computational chemistry, many synthetic analogs with improved biological properties have been obtained. Data from in vitro and in vivo experiments strongly suggest synthetic derivatives as promising candidates in the chemopreventive and chemotherapeutic strategies.