• Title/Summary/Keyword: inhibition of DNA damage

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DNA Damage of Lipid Oxidation Products and Its Inhibition Mechanism (지질산화생성물의 DNA손상작용 및 그 억제기구)

  • KIM Seon-Bong;KANG Jin-Hoon;PARK Young-Ho
    • 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.

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DNA Damage Protection and Anti-inflammatory Activity of Different Solvent Fractions from Aruncus dioicus var. kamtschaticus

  • Zhang, Qin;Kim, Hye-Young
    • Korean Journal of Plant Resources
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    • v.27 no.6
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    • pp.714-719
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    • 2014
  • This study investigated DNA damage protection and anti-inflammatory activity of different solvent fractions from Aruncus dioicus var. kamtschaticus (A. dioicus) aerial parts water extract. As for DNA damage protection, distilled water ($H_2O$) fraction displayed the most powerful protection for DNA damage at a concentration of 1 mg/ml. As for anti-inflammatory activity, dichloromethane ($CH_2Cl_2$) fraction exhibited the highest NO inhibition activity, ranging from 61% to 19% ($10-40{\mu}g/ml$). Furthermore, the levels of pro-inflammatory cytokines mRNA expressions and intracellular reactive oxygen species (ROS) were employed to verify the anti-inflammatory activity of the $CH_2Cl_2$ fraction on further researches. It could be concluded that A. dioicus had a significantly effect of DNA damage protection and anti-inflammatory activity which also as an essential edible vegetable and medicinal species.

Inhibition Effects of Persicaria amphibia (L.) Delarbre on Oxidative DNA Damage via ATM/Chk2/p53 pathway

  • So-Yeon Han;Hye-Jeong Park;Jeong-Yong Park;Seo-Hyun Yun;Mi-Ji Noh;Soo-Yeon Kim;Tae-Won Jang;Jae-Ho Park
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2021.04a
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    • pp.52-52
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    • 2021
  • Persicaria amphibia as an England native plant, is a rhizomatous perennial, one of the rather amphibious plants. Its aquatic form contains water-soluble sugars, starch, and protein. P. amphibia have up to 18% tannins in stems and rhizomes. Previous studies have confirmed the anti-inflammatory activity of live bacteria roots, but no studies on bioactivity are known. DNA damage responses (DDRs) pathways are considered a crucial factor affecting the alleviation of cellular damage. The ataxia-telangiectasia mutated and Rad3 related (ATM) and checkpoint kinase 2 (Chk2) pathways are the main pathways of DNA damage response. Also, p53 is a key integrator of cellular response to oxidative DNA damage, contributing repair, or leading transcription including apoptosis. In the present study, we conducted an investigation into the inhibitory effects of P. amphibia on oxidative DNA damage for confirming potential to complementary medicine and therapies. In conclusion, P. amphibia can provide protective effects against double-stranded DNA break (DSB) caused by oxidative DNA damage.

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Antioxidative Activities and Inhibition Effects on Oxidative DNA Damage of Valeriana fauriei (쥐오줌풀의 항산화 및 산화적 DNA 손상 억제 활성)

  • Park, Jae Ho;Jang, Tae Won;Lee, Seung Hyun
    • Korean Journal of Medicinal Crop Science
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    • v.24 no.6
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    • pp.464-470
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    • 2016
  • Background: Valeriana fauriei (Valerianaceae) has been used to as a traditional medicine to treat a variety of symptoms, including headache, insomnia, hypertension, and menstrual irregularity. However, the present study investigates the species' antioxidant activity and its inhibition of oxidative DNA damage, which have yet to be studied. Methods and Results: The antioxidant activity was assessed using radical scavenging assays with 1,1-diphenyl-2-picryl hydrazyl (DPPH) and, 2, 2'-azino-bis (3-ethylbenzothiazoline-6 sulfonic acid) diammonium salt (ABTS) and a reducing power assay. The total phenol content was also analyzed, and phenolic compounds were detected using HPLC/UV, whereas the inhibitory effect of Valeriana fauriei on oxidative DNA damage was measured using ${\phi}-174$ RF I plasmid DNA cleavage assay. The DPPH and ABTS radical scavenging activity were $75.17{\pm}3.55%$ and $95.83{\pm}0.63%$, repectively, and the reducing power was $93.14{\pm}1.74$ at $200{\mu}g/m{\ell}$. The total phenol content was $10.24{\pm}0.04mg/g$, whereas chlorogenic acid, catechin, caffeic acid and epicatechin were identified using HPLC/UV, and the ${\phi}-174$ RF I plasmid DNA cleavage assay indicated that V. fauriei provided protection against oxidative damage. Conclusions: The results of the present study suggest that V. fauriei has powerful antioxidant activity that can provide protective effects against the oxidative DNA damage caused by free radicals. The species, therefore, provides a valuable resource for the development of natural pharmaceutical to treat aging, cancer, and degenerative diseases.

Protective Effects of Nypa fruticans Wurmb against Oxidative DNA Damage and UVB-induced DNA Damage

  • So-Yeon Han;Tae-Won Jang;Da-Yoon Lee;Seo-Yoon Park;Woo-Jin Oh;Se Chul Hong;Jae-Ho Park
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2023.04a
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    • pp.54-54
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    • 2023
  • Nypa fruticans Wurmb (N. fruticans) is a plant that belongs to Araceae and N. fruticans is mainly found in tropical mangrove systems. The parts (leaves, stems, and roots) of N. fruticans are traditionally used for asthma, sore throat, and liver disease. N. fruticans contains flavonoids and polyphenols, which are substances that have inhibitory effects on cancer and oxidant. In previous studies, some pharmaceutical effects of N. fruticans on melanogenesis and inflammation have been reported. The present study is conducted to investigate the effect of the ethyl acetate fraction of N. fruticans (ENF) on oxidative DNA damage and UVB-induced DNA damage. DNA damage response (DDR) pathway is important in research on cancer, apoptosis, and so on. DDR pathways are considered a crucial factor affecting the alleviation of cellular damage. ENF could reduce oxidative DNA damage derived from reactive oxygen species by the Fenton reaction. Also, ENF reduced the intensity of intracellular ROS in the live cell image by DCFDA assay. UVB is known to cause skin and cellular damage, then finally contribute to causing the formation of tumors. As for the strategies of reducing DNA damage by UVB, inhibition of p53, H2AX, and Chk2 can be important indexes to protect the human body from DNA damage. As a result of confirming the protective effect of ENF for UVB damage, MMPs significantly decreased, and the expression of apoptosis-related factors tended to decrease. In conclusion, ENF can provide protective effects against double-stranded DNA break (DSB) caused by oxidative DNA damage and UVB-induced DNA damage. These results are considered to be closely related to the protective effect against radicals based on catechin, epicatechin, and isoquercitrin contained in ENF. Based on these results, it is thought that additional mechanism studies for inhibiting cell damage are needed.

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Chemopreventive Effect of Quercetin, Vitamin C and Trolox Against the Organic Extract of Airborne Particulate Matter Induced Genotoxicity in A549 Human Lung Carcinoma Cells (대기부유분진추출물로 야기된 DNA 손상에 대한 Quercetin, Vitamin C 및 Trolox 의 보호효과)

  • Kim, Nam-Yee;Heo, Moon-Young
    • YAKHAK HOEJI
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    • v.51 no.4
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    • pp.239-245
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    • 2007
  • In order to evaluate the genotoxicity of airborne particulate matter extracted with dichloromethane (APE), the rat microsome mediated (S-9) or DNA repair enzyme treated Comet assays were performed using the single cell gel electrophoresis in A549 human lung carcinoma cells. It was found that the cells interacting with APE showed more DNA single-strand breaks relative to untreated cells. The genotoxicity of APE was increased with the treatment of S-9 mixture. Microsome mediated DNA damage was inhibited by CYP1Al inhibitor, quercetin. The APE also showed oxidative DNA damage evaluated by endonuclease III treatment. Oxidative DNA damage of APE was inhibited by antioxidants such as vita- min C and Trolox. We also found that the vegetables or fruits extract may reduce APE-induced genotoxicity by their anti- oxidant activity and CYP1A1 inhibition.

Protective Effect of Crataegus pinnatifida and Cinnamomum cassia on Ethanol-induced Cytotoxicity and DNA Damage in HepG2 Cells

  • Kim, Nam Yee;Song, Eun Jeong;Heo, Moon Young
    • Natural Product Sciences
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    • v.20 no.4
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    • pp.237-242
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    • 2014
  • Plant extracts produced from branches of Crataegus pinnatifida and barks of Crataegus pinnatifida inhibited ethanol-induced cytotoxicity and DNA damage in liver cells. Furthermore, these two extracts inhibited the expression and activities of CYP2E1 enzyme. Cinnamomum cassia had a better effect on inhibition of DNA damage than Crataegus pinnatifida, as well as showed a high tendency to inhibit CYP2E1 expression and catalytic activities. It is considered that extracts produced from Crataegus pinnatifida or Cinnamomum cassia have an effect to reduce ethanol-induced cytotoxicity and DNA damage in liver cells. Therefore, we suggest to use Crataegus pinnatifida and Cinnamomum cassia and their ingredients as potential candidate substances to prevent and treat ethanol-induced cytotoxicity and genotoxicity in liver cells.

Effect of Some Natural Products on the DNA Damaging Activity of 4NQO (4-nitroquinoline n-oxide) and Daunorubicin (Daunorubicin과 4NQO의 DNA damaging activity에 대한 천연물질의 영향)

  • 이완희;이행숙;권혁일;박진서;최수영;이길수
    • Environmental Mutagens and Carcinogens
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    • v.19 no.2
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    • pp.112-115
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    • 1999
  • The action mechanism of the inhibitory effect of some natural products on the DNA strand break and DNA damage was investigated in vitro and in vivo. In the E. coli chromosomal DNA strand break experiment in vitro, three mushroom water extracts were effective on the DNA strand breaking by daunorubicin. Phellinus linteus water extract inactivated daunorubicin, a DNA strand breaking agent, but did not protect DNA from daunorubicin-induced DNA strand breaking. Agaricus blazei water extract inhibited DNA strand breaking action of daunorubicin not only by daunorubicin inactivation, but also by DNA protection from daunorubicin. An inhibitory effect of Ganoderma lucidum water extract on the DNA strand break was based on the DNA protection rather than daunorubicin inactivation. In vivo mutagen assay system (SOS-chromotest), among three mushroom water extracts Phellinus linteus water extract was the most effective one on the inhibition of DNA damage by 4-NQO. The results suggest that all three mushroom water extracts inhibit daunorubicin-induced DNA damage and in vivo DNA damaging action of 4-NQO by the reaction of mutagen inactivation or DNA protection from the mutagen.

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Interferon-Stimulated Gene 15 in the Control of Cellular Responses to Genotoxic Stress

  • Jeon, Young Joo;Park, Jong Ho;Chung, Chin Ha
    • Molecules and Cells
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    • v.40 no.2
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    • pp.83-89
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    • 2017
  • Error-free replication and repair of DNA are pivotal to organisms for faithful transmission of their genetic information. Cells orchestrate complex signaling networks that sense and resolve DNA damage. Post-translational protein modifications by ubiquitin and ubiquitin-like proteins, including SUMO and NEDD8, are critically involved in DNA damage response (DDR) and DNA damage tolerance (DDT). The expression of interferon-stimulated gene 15 (ISG15), the first identified ubiquitin-like protein, has recently been shown to be induced under various DNA damage conditions, such as exposure to UV, camptothecin, and doxorubicin. Here we overview the recent findings on the role of ISG15 and its conjugation to target proteins (e.g., p53,$ {\Delta}Np63{\alpha}$, and PCNA) in the control of cellular responses to genotoxic stress, such as the inhibition of cell growth and tumorigenesis.

Identification of Protein Phosphatase 4 Inhibitory Protein That Plays an Indispensable Role in DNA Damage Response

  • Park, Jaehong;Lee, Jihye;Lee, Dong-Hyun
    • Molecules and Cells
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    • v.42 no.7
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    • pp.546-556
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    • 2019
  • Protein phosphatase 4 (PP4) is a crucial protein complex that plays an important role in DNA damage response (DDR), including DNA repair, cell cycle arrest and apoptosis. Despite the significance of PP4, the mechanism by which PP4 is regulated remains to be elucidated. Here, we identified a novel PP4 inhibitor, protein phosphatase 4 inhibitory protein (PP4IP) and elucidated its cellular functions. PP4IP-knockout cells were generated using the CRISPR/Cas9 system, and the phosphorylation status of PP4 substrates (H2AX, KAP1, and RPA2) was analyzed. Then we investigated that how PP4IP affects the cellular functions of PP4 by immunoprecipitation, immunofluorescence, and DNA double-strand break (DSB) repair assays. PP4IP interacts with PP4 complex, which is affected by DNA damage and cell cycle progression and decreases the dephosphorylational activity of PP4. Both overexpression and depletion of PP4IP impairs DSB repairs and sensitizes cells to genotoxic stress, suggesting timely inhibition of PP4 to be indispensable for cells in responding to DNA damage. Our results identify a novel inhibitor of PP4 that inhibits PP4-mediated cellular functions and establish the physiological importance of this regulation. In addition, PP4IP might be developed as potential therapeutic reagents for targeting tumors particularly with high level of PP4C expression.