• Title/Summary/Keyword: cellular damage

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Fermented ginseng, GBCK25, ameliorates steatosis and inflammation in nonalcoholic steatohepatitis model

  • Choi, Naeun;Kim, Jong Won;Jeong, Hyeneui;Shin, Dong Gue;Seo, Jeong Hun;Kim, Jong Hoon;Lim, Chae Woong;Han, Kang Min;Kim, Bumseok
    • Journal of Ginseng Research
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    • v.43 no.2
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    • pp.196-208
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    • 2019
  • Background: Nonalcoholic steatohepatitis (NASH) is one of the chronic inflammatory liver diseases and a leading cause of advanced liver fibrosis, cirrhosis, and hepatocellular carcinoma. The main purpose of this study was to clarify the effects of GBCK25 fermented by Saccharomyces servazzii GB-07 and pectinase, on NASH severity in mice. Methods: Six-wk-old male mice were fed either a normal diet (ND) or a Western diet (WD) for 12 wks to induce NASH. Each group was orally administered with vehicle or GBCK25 once daily at a dose of 10 mg/kg, 20 mg/kg, 100 mg/kg, 200 mg/kg, or 400 mg/kg during that time. The effects of GBCK25 on cellular damage and inflammation were determined by in vitro experiments. Results: Histopathologic analysis and hepatic/serum biochemical levels revealed that WD-fed mice showed severe steatosis and liver injury compared to ND-fed mice. Such lesions were significantly decreased in the livers of WD-fed mice with GBCK25 administration. Consistently, mRNA expression levels of NASH-related inflammatory-, fibrogenic-, and lipid metabolism-related genes were decreased in the livers of WD-fed mice administered with GBCK25 compared to WD-fed mice. Western blot analysis revealed decreased protein levels of cytochrome P450 2E1 (CYP2E1) with concomitantly reduced activation of c-Jun N-terminal kinase (JNK) in the livers of WD-fed mice administered with GBCK25. Also, decreased cellular damage and inflammation were observed in alpha mouse liver 12 (AML12) cells and RAW264.7 cells, respectively. Conclusion: Administration of GBCK25 ameliorates NASH severity through the modulation of CYP2E1 and its associated JNK-mediated cellular damage. GBCK25 could be a potentially effective prophylactic strategy to prevent metabolic diseases including NASH.

The Expression of DNA Polymerase-$\beta$ and DNA Damage in Jurkat Cells Exposed to Hydrogen Peroxide under Hyperbaric Pressure

  • Sul, Dong-Geun;Oh, Sang-Nam;Lee, Eun-Il
    • Molecular & Cellular Toxicology
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    • v.4 no.1
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    • pp.66-71
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    • 2008
  • Long term exposure of Jurkat cells to 2 ATA pressure resulted in the inhibition of cell growth. Under a 2 ATA pressure, the morphological changes in the cells were visualized by electron microscopy. The cells exhibited significant inhibitory responses after three passages. However, short-term exposure study was carried out, 2 ATA pressure may have beneficial effects. The Jurkat cells were exposed to $H_2O_2$ (25 and $50{\mu}M$) in order to induce DNA damage, and then incubated under at either normal pressure or 2 ATA for 1 or 2 hours in order to recover the DNA damage. The extent of DNA damage was determined via Comet assay. More recovery from DNA damage was observed at 2 ATA than at normal pressure. The activity of the DNA repair enzymes, DNA polymerase-$\beta$, was also evaluated at both normal pressure and 2 ATA. The activity of DNA polymerase-$\beta$ was observed to have increased significantly at the 2 ATA than at normal pressure. In conclusion, the effects of hyperbaric pressure from 1 ATA to 2 ATA on biochemical systems can be either beneficial or harmful. Long term exposure to hyperbaric pressure clearly inhibited cell proliferation and caused genotoxic effects, but short-term exposure to hyperbaric pressure proved to be beneficial in terms of bolstering the DNA repair system. The results of the present study have clinical therapeutic application, and might prove to be an useful tool in the study of genotoxicity in the future.

The Effect of Green Vegetable Drink Supplementation on Cellular DNA Damage and Antioxidant Status of Korean Smokers (녹즙혼합음료 섭취가 흡연자의 임파구 DNA 손상 및 혈장 항산화 영양상태에 미치는 영향)

  • Kim Hye-Young;Park Yoo Kyoung;Kim Tae Seok;Kang Myung-Hee
    • Journal of Nutrition and Health
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    • v.39 no.1
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    • pp.18-27
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    • 2006
  • Smoking is well known to be associated with increased indices of tree radical-mediated damage of DNA, indicating that smoking may exacerbate the initiation and propagation of oxidative stresses, which are potential underlying processes in the pathogenesis of many diseases. The purpose of this study was to evaluate whether a daily regimen of green vegetable drink supplementation to smokers can be protective against endogenous lymphocytic DNA damage and whether it could enhance other antioxidant status. Twenty nonsmokers and nineteen smokers aged 23-60 were given 240 ml of green vegetable drink every day for 8 weeks in addition to their normal diet, and blood samples were drawn before and after the intervention. The 8 weeks of green vegetable drink consumption resulted in a significant decrease (p = 0.000, by paired t-test) in lymphocyte DNA damage expressed by TL (before: $63.13{\pm}1.05$ vs after: $37.86{\pm}10.83$, before: $66.73{\pm}1.24$ vs after: $36.51{\pm}1.13$), TM (before: $14.55{\pm}0.61$ vs after: $6.61{\pm}0.25$, before: $15.36{\pm}0.45$ vs after: $6.65{\pm}0.38$) and $\%$ DNA in tail (before: $19.7{\pm}0.41$ vs after: $16.6{\pm}0.37$, before: $20.6{\pm}0.31$ vs after: $17.1{\pm}0.5$) in both nonsmokers and smokers respectively. Vitamin C and TRAP level was not significantly changed after the supplementation. In conclusion, these results support the hypothesis that green vegetable drink exert a cancer-protective effect partially via a decrease in oxidative damage to DNA.

PCNA Modifications for Regulation of Post-Replication Repair Pathways

  • Lee, Kyoo-young;Myung, Kyungjae
    • Molecules and Cells
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    • v.26 no.1
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    • pp.5-11
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    • 2008
  • Stalled DNA replication forks activate specific DNA repair mechanism called post-replication repair (PRR) pathways that simply bypass DNA damage. The bypassing of DNA damage by PRR prevents prolonged stalling of DNA replication that could result in double strand breaks (DSBs). Proliferating cell nuclear antigen (PCNA) functions to initiate and choose different bypassing pathways of PRR. In yeast, DNA replication forks stalled by DNA damage induces monoubiquitination of PCNA at K164, which is catalyzed by Rad6/Rad18 complex. PCNA monoubiquitination triggers the replacement of replicative polymerase with special translesion synthesis (TLS) polymerases that are able to replicate past DNA lesions. The PCNA interaction motif and/or the ubiquitin binding motif in most TLS polymerases seem to be important for the regulation of TLS. The TLS pathway is usually error-prone because TLS polymerases have low fidelity and no proofreading activity. PCNA can also be further polyubiquitinated by Ubc13/ Mms2/Rad5 complex, which adds an ubiquitin chain onto monoubiquitinated K164 of PCNA. PCNA polyubiquitination directs a different PRR pathway known as error-free damage avoidance, which uses the newly synthesized sister chromatid as a template to bypass DNA damage presumably through template switching mechanism. Mammalian homologues of all of the yeast PRR proteins have been identified, thus PRR is well conserved throughout evolution. Mutations of some PRR genes are associated with a higher risk for cancers in mice and human patients, strongly supporting the importance of PRR as a tumor suppressor pathway.

Bambusae Calulis in Liquamen (Jukryuk) and Zingiberis Rhizoma Juice's (Saengkang- juice's) Effect on Ischemic Damage Secondary to MCA Occlusion in Mice (죽력과 생강즙이 중대뇌동맥 폐쇄에 의한 뇌허혈 손상에 미치는 영향)

  • 류주열;김영균;권정남
    • The Journal of Korean Medicine
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    • v.23 no.3
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    • pp.134-144
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    • 2002
  • Objective : The purpose of this study was to investigate the effect of Jukryuk and Saengkang-juices on cerebral vascular ischemia (CVI) of the middle cerebral artery (MCA). Method : By admiuistration Jukryuk and Saengkang-juices, we compared treated groups with untreated groups, in view of five points as follows: 1) cerebral damage; 2) damaged area of ischemia; 3) cerebral edema; 4) the number of neuronal cells adjacent to the areas damaged by ischemia; and 5) the number of neuronal cells adjacent to the areas damaged by ischemia Results : In this experiment, the effect of Jukryuk and Saengkang-juices was determined by inducing cerebral vascular ischemia after occluding the middle cerebral artery (MCA) in mice, and making observations and comparisons such as alterations in damaged areas and neuronal cellular changes in the brain. Conclusions : According to the above results, Jukryuk and Saengkang-juices can protect the cerebral vascular ischemia.

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Biocide sodium hypochlorite decreases pigment production and induces oxidative damage in the harmful dinoflagellate Cochlodinium polykrikoides

  • Ebenezer, Vinitha;Ki, Jang-Seu
    • ALGAE
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    • v.29 no.4
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    • pp.311-319
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    • 2014
  • The biocide sodium hypochlorite (NaOCl) is widely used for controlling algal growth, and this application can be extended to marine environments as well. This study evaluates the biocidal efficiency and cellular toxicity of NaOCl on the harmful dinoflagellate Cochlodinium polykrikoides, with emphasis on pigment production and antioxidant enzyme activity. The test organism showed dose-dependent decrease in growth rate on exposure to NaOCl, and the 72 h $EC_{50}$ was measured to be $0.584mg\;L^{-1}$. NaOCl significantly decreased pigment levels and chlorophyll autofluorescence intensity, indicating possible detrimental effects on the photosystem of C. polykrikoides. Moreover, it significantly increased the activities of antioxidant enzymes, suggesting the production of reactive oxygen species in the cells. These data indicate that NaOCl exerted deleterious effects on the photosynthetic machinery and induced oxidative damage in the dinoflagellate and this biocide could be effectively used for the control of algal blooms.

COMBINED IN VITRO ASSAY FOR 3T3 NRU PT ASSAY AND PHOTOHEMOLYSIS AS PART OF PHOTOTOXICITY TEST

  • Chunja Nam;Kim, Baehwan;Lee, Byoungseok;Seongjoon Moon;Ihseop Chang
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2001.05a
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    • pp.117-117
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    • 2001
  • The aim of this study was to assess a possible alternative method as replacement for in vivo phototoxicity test. The 3T3 mouse fibroblast neutral red uptake phototoxicity assay (3T3 NRU PT assay) is a screening method for studying DNA or cellular damage. Photohemolysis assay is a mechanistic study for investigating oxygen-dependent membrane damage.(omitted)

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The Effect of Tryptophan Administration on the Plasma Free Amino Acid Concentration, Liver Microsomal Cytochrome P450 Content and Cellular Structure of Rats Consumed Reserpine and Low Protein Diet with Different Carbohydrate Contents (Tryptophan 투여가 Reserpine과 식이 탄수화물 수준이 다른 저단백식이를 섭취한 흰쥐의 혈장 아미노산 농도, 간 Cytochrome P450 함량 및 간세표 미세구조에 미치는 영향)

  • 신동순
    • Journal of Nutrition and Health
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    • v.29 no.7
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    • pp.689-702
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    • 1996
  • The purpose of this experiment was to compare the effects of tryptophan administration on nutritional status of female rats which consumed reserpine and 6% casein diet with different carbohydrate contents(87%, 65%, 44% respective). Final body weight, body weight gain, FER, plasma amino acid concentration and microsomal cytochrome P 450 content in liver were measured and microscopic structure of hepatocytes was observed. In low-protein diet, the higher the carbohydrate content of diet was, the lower the damage was in the rat's liver. Tryptophan administration after dose of reserpine induced more effective recovery from liver damage of rats in high carbohydrate diet group than that in low carbohydrate diet group. In conclusion, the general nutritional assessments such as final body weight and body weight gain provided better estimate of the degree of structural changes in hepatocytes than functional assessment such as plasma amino acid concentration or liver microsomal cytochrome P450.

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Isolation and Characterization of New Family Genes of DNA Damage in Fission Yeast

  • Choi, In-Soon
    • Environmental Mutagens and Carcinogens
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    • v.19 no.1
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    • pp.28-33
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    • 1999
  • The SNF2 family includes proteins from a variety of species with roles I cellular processes such as transcriptional regulation, recombination and various types of DNA repair. Several proteins with unknown function are also included in this family. Here, we report the cloning and characterization of hrp 2+ gene (helicase related gene from S. pombe) which was isolated by PCR amplication using the conserved domain of SNF2 motifs within the ERCC6 gene which encodes a protein involved in DNA excision repair. The hrp2+ gene was isolated by screening with yeast S. pombe genomic library. The isolated cloned contained 6.5 kb insert DNA. Southern blot analysis confirmed that S. pombe chromosome contains the same DNA as hrp2+ gene and this gene exists as a single copy in S. pombe genome. The 4.7 kb transcript of mRNA was identified by Northern blot. To examined the transcriptional regulation of hrp2+ gene, DNA damaging agents were treated. These results indicated that the hrp2+ gene may not be directly involved in DNA replication, but may be involved in damage response pathway.

OXIDATIVE DAMAGE, DNA REPAIR AND SIGNAL TRANSDUCTION IN CHEMICAL TERATOGENESIS.

  • Peter G Wells;Yadvinder Bhuller;Connie S Chen;Jeffrey T Henderson;Winnie Jeng;Sonja Kasapinovic;Julia C Kennedy;Rebecca R Laposa;Christopher J Nicol;Toufan Parman;Michael J Wiley;Louise M Winn;Andrea W Wong
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.05a
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    • pp.44-64
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    • 2002
  • Embryonic prostaglandin H synthases (PHSs) and lipoxygenases bioactivate xenobiotics (phenytoin, thalidomide, benzo[a]pyrene) to free radical intermediates that initiate reactive oxygen species (ROS) formation, which oxidatively damage cellular macromolecules and/or alter signal transduction.(omitted)

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