• BMB Reports
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• v.47 no.11
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• pp.609-618
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• 2014

DNA methylation at cytosines (5mC) is a major epigenetic modification involved in the regulation of multiple biological processes in mammals. How methylation is reversed was until recently poorly understood. The family of dioxygenases commonly known as Ten-eleven translocation (Tet) proteins are responsible for the oxidation of 5mC into three new forms, 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). Current models link Tet-mediated 5mC oxidation with active DNA demethylation. The higher oxidation products (5fC and 5caC) are recognized and excised by the DNA glycosylase TDG via the base excision repair pathway. Like DNA methyltransferases, Tet enzymes are important for embryonic development. We will examine the mechanism and biological significance of Tet-mediated 5mC oxidation in the context of pronuclear DNA demethylation in mouse early embryos. In contrast to its role in active demethylation in the germ cells and early embryo, a number of lines of evidence suggest that the intragenic 5hmC present in brain may act as a stable mark instead. This short review explores mechanistic aspects of TET oxidation activity, the impact Tet enzymes have on epigenome organization and their contribution to the regulation of early embryonic and neuronal development.

• Food Science and Biotechnology
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• v.18 no.1
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• pp.130-136
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• 2009

The present study was conducted to determine the protective ability of the ethanol extracts of Hypericum scabroides Robson & Poulter (HS) and Hypericum triquetrifolium Turra (HT) against the protein oxidation and DNA damage induced by Fenton system. The ability of HS and HT to prevent oxidative damage to bovine serum albumin (BSA) induced by $Fe^{3+}/H_2O_2$ and ascorbic acid was investigated. The ethanol extracts of HS and HT at different concentrations ($50-1,000{\mu}g/mL$) efficiently prevented protein oxidation induced by hydroxy radical as assayed by protein oxidation markers including protein carbonyl formation (PCO) and polyacrylamide gel electrophoresis. The effect of ethanol extracts of HS and HT on DNA cleavage induced by UV-photholysis of $H_2O_2$ using pBluescript M13+ plasmid DNA were investigated. These extracts significantly inhibited DNA damage induced by reactive oxygen species (ROS). Therefore, HS and HT extracts may be useful in the food industry as effective synthetic antioxidants.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.20 no.5
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• pp.419-430
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• 1987

The damage of plasmid DNA by lipid peroxidation and its inhibition were investigated through the model system of DNA and linoleic acid at $37^{\circ}C$. The degree of DNA damage increased in proportion to the increase of concentration and peroxidation of linoleic acid. DNA damage induced from linoleic acid peroxidation was greatly inhibited by the addition of active oxygen scavengers, especially, singlet of oxygen scavenge$(\alpha-tocopherol,\;cysteine)$ and superoxide anion scavenger(superoxide dismutase, ascorbic acid) in reaction system. These active oxygens, such as superoxide anion and hydrogen peroxide were rapidly generated in the early stage of peroxidation (POV below 100 mg/kg) and also scanvenged by the addition of superoxide dismutase and catalase, respectively. Hydroperoxide isolated from autoxidised linoleic acid showed DNA damage. Hydroperoxide induced-DNA damage was not inhibited by active oxygen scavengers. Lipid oxidation products, malonaldehyde and hexanal, also influenced on the DNA damage. Accordingly, it is speculated that DNA damage by lipid oxidation products is due to active oxygens such as singlet oxygen and superoxide anion formed in the early stage of peroxidation, direct action of hydroperoxide and formation of low molecular carbonyl compound-DNA complex. Furthermore, DNA damage induced by lipid peroxidation was remarkably inhibited by the addition of active oxygen scavengers and natural antioxidative fractions extracted from garlic and ginger. These antioxidative fractions also suppressed the generation of active orygens and linoleic acid oxidation. It is assumed that the inhibition of DNA damage by garlic and ginger extracts is due to the scavenging effect of active oxygens and the inhibition of hydroperoxide and oxidation products formation.

• Bulletin of the Korean Chemical Society
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• v.26 no.8
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• pp.1251-1254
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• 2005

It has been proposed that oxidation of L-3,4-dihydroxyphenylalanine (DOPA) may contribute to the pathogenesis of neurodegenerative disease. In this study, L-DOPA-Fe(III)-mediated DNA cleavage and the protection by carnosine and homocarnosine against this reaction were investigated. When plasmid DNA was incubated with L-DOPA in the presence of Fe(III), DNA strand was cleaved. Radical scavengers and catalase significantly inhibited the DNA breakage. These results suggest that $H_2O_2$ may be generated from the oxidation of DOPA and then $Fe^{3+}$ likely participates in a Fenton’s type reaction to produce hydroxyl radicals, which may cause DNA cleavage. Carnosine and homocarnosine have been proposed to act as anti-oxidants in vivo. The protective effects of carnosine and homocarnosine against L-DOPA-Fe(III)-mediated DNA cleavage have been studied. Carnosine and homocarnosine significantly inhibited DNA cleavage. These compounds also inhibited the production of hydroxyl radicals in L-DOPA/$Fe^{3+}$ system. The results suggest that carnosine and homocarnosine act as hydroxyl radical scavenger to protect DNA cleavage. It is proposed that carnosine and homocarnosine might be explored as potential therapeutic agents for pathologies that involve damage of DNA by oxidation of DOPA.

• Preventive Nutrition and Food Science
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• v.14 no.4
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• pp.277-282
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• 2009

The antioxidant potency of methanolic extract of Duchesnea indica (MDI; Indian strawberry) was investigated by employing various established in vitro systems, such as total phenolic content, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging activity, reducing power assay, metal chelating assay, superoxide radical scavenging activity and protective ability of DNA damage and protein oxidation. MDI inhibited metal chelating by 75.57% at 2 mg/mL, scavenged 50% DPPH free radical at 29.13 ${\mu}$g/mL, and eliminated approximately 46.21% superoxide radical at the concentration of 1 mg/mL. In addition, MDI showed strong ability on reducing power, DNA damage protection and protein oxidation protection. Overall, results suggested that MDI might be beneficial as a potent antioxidant and effectively employed as an ingredient in food applications.

• Bulletin of the Korean Chemical Society
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• v.33 no.4
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• pp.1290-1296
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• 2012

Fenton reaction and iron autoxidation have been debated for the major process in ROS mediated DNA cleavage. We compared both processes on iron oxidation, DNA cleavage, and cyclic voltammetric experiment at different pHs. Both oxidation reactions were preferred at basic pH condition, unlike DNA cleavage. This indicates that iron oxidation and the following steps probably occur separately. The ROS generated from autoxidation seems to be superoxide radical since sod exerted the best inhibition on DNA cleavage when $H_2O_2$ was absent. In comparison of cyclic voltammograms of $Fe^{2+}$ in NaCl solution and phosphate buffer, DNA addition to phosphate buffer induced significant change in the redox cycle of iron, indicating that iron may bind DNA as a complex with phosphate. Different pulse voltammogram in the presence of ctDNA suggest that iron ions are recyclable at acidic pH, whereas they may form an electrically stable complex with DNA at high pH condition.

• BMB Reports
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• v.28 no.3
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• pp.249-253
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• 1995

The nonenzymatic glycation of copper, zinc-superoxide dismutase (Cu,Zn-SOD) led to inactivation and fragmentation of the enzyme. The glycated Cu,zn-SOD was isolated by boronate affinity chromatography. The formation of 8-hydroxy-2'-deoxyguanosine (8-OH-dG) in calf thymus DNA and the generation of strand breaks in pBhiescript plasmid DNA by a metal-catalyzed oxidation (MCO) system composed of $Fe^{3+}$, $O_2$, and glutathione (GSH) as an electron donor was enhanced more effectively by the glycated CU,Zn-SOD than by the nonglycated enzyme. The capacity of glycated Cu,Zn-SOD to enhance damage to DNA was inhibited by diethylenetriaminepentaacetic acid (DETAPAC), azide, mannitol, and catalase. These results indicated that incubation of glycated CU,Zn-SOD with GSH-MCO may result in a release of $Cu^{2+}$ from the enzyme. The released $Cu^{2+}$ then likely participated in a Fenton-type reaction to produce hydroxyl radicals, which may cause the enhancement of DNA damage.

• BMB Reports
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• v.36 no.1
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• pp.12-19
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• 2003

Fragmentation of purine imidazole ring and production of formamidopyrimidines in deoxynucleosides (Fapy lesions) occurs upon DNA oxidation as well as upon spontaneous or alkali-triggered rearrangement of certain alkylated bases. Many chemotherapeutic agents such as cyclophosphamide or thiotepa produce such lesions in DNA. Unsubstituted FapyA and FapyG, formed upon DNA oxidation cause moderate inhibition of DNA synthesis, which is DNA polymerase and sequence dependent. Fapy-7MeG, a methylated counterpart of FapyG-, a efficiently inhibits DNA replication in vitro and in E.coli, however its mutagenic potency is low. This is probably due to preferential incorporation of cytosine opposite Fapy-7MeG and preferential extension of Fapy-7MeG:C pair. In contrast, FapyA and Fapy-7MeA possess miscoding potential. Both lesions in SOS induced E.coli preferentially mispair with cytosine giving rise to A$\rightarrow$G transitions. Fapy lesions substituted with longer chain alkyl groups also show simult aneous lethal and mutagenic properties. Fapy lesions are actively eliminated from DNA by repair glycosylases specific for oxidized purines and pyrimidines both in bacteria and eukaryotic cells. Bacterial enzymes include E.coli formamidopyrimidine-DNA-glycosylase (Fpg protein), endonuclease III (Nth protein) and endonuclease VIII (Nei protein).

• Proceedings of the Korean Society of Potoscience Conference
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• 2005.06a
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• pp.18-18
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• 2005

• The Korean Journal of Food And Nutrition
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• v.8 no.2
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• pp.135-144
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• 1995

Lipid oxidation in foods produce the peroxidation products, toxic substance and rancidity odor. In vivo, lipid peroxidation by free radicals or molecular singlet oxygen cause such as a damage of DNA, cancer and aging. Accordingly, the development of new compound Inhibit lipid oxidation in foods and in vivo is very important. Antioxidants are generally used as a protection material of oxidation for a storage and preservation of foods. In terms of stability of foods and health for human, development of high effective antioxidants In a nature is required. In this point of view, this paper presents the research trends of a kind of natural antioxidative substances and its antioxidative activity.