• 제목/요약/키워드: GPX1

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Anticancer Activity of Monoterpenes and the Changes of Enzymes Activities Responsible for the Conversion of Reactive Oxygen Species (Monoterpenes의 항암작용과 활성산소 전환 효소의 활성 변화)

  • 조용선;김수진;박시원
    • YAKHAK HOEJI
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    • 제47권1호
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    • pp.37-45
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    • 2003
  • The present study was undertaken to investigate the anticancer activity of monoterepenes in the animal and the cancer cell line tests. Both of the noncyclic and cyclic monoterpenes showed significant life prolonging effects on ICR mouse with abdominal cancer induced by Sarcoma 180 cells up to 67.4% and 63.5% in case of linalool and geraniol, respectively. Linalool and geraniol also exhibited very excellent cytotoxicity against L1210 leukemic cells with $IC_{50}$/ value of 0.32 $\mu\textrm{g}$/mι in 5 days culture condition. In the presence of linalool and geraniol, the generation of $O_2$$^{[-10]}$ ion were found to be increased proportionally to the cytotoxicity arisen from these monoterpenes. Furthermore, the antioxidant enzymes activities such as superoxide dismutase (SOD) and glutathione peroxidase (GPx) responsible for the conversion of $O_2$$^{[-10]}$ ion to $H_2O$$_2$ and then to $H_2O$ augmented remarkably by linalool and geraniol. All data put together it can be postulated that monoterpenes may kill abdominal cancer cells of ICR mouse probably by activating anticancer system of the body, whereas the death of L1210 cells may be due to the detrimental attacks of reactive oxygen species (ROS) including $O_2$$^{[-10]}$ in spite of antioxidant enzymes activities to overcome the ROS attacks.

Analysis of Genes Regulated by HSP90 Inhibitor Geldanamycin in Neurons

  • Yang, Young-Mo;Kim, Seung-Whan;Kwon, O-Yu
    • Biomedical Science Letters
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    • 제15권1호
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    • pp.97-99
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    • 2009
  • Geldanamycin is a benzoquinone ansamycin antibiotic that binds to cytosol HSP90 (Heat Shock Protein 90) and changes its biological function. HSP90 is involved in the intracellular important roles for the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis. To identify genes expressed during geldanamycin treatment against neurons of rats (PC12 cells), DNA microarray method was used. We have isolated 2 gene groups (up-or down-regulated genes) which are geldanamycin differentially expressed in neurons. Granzyme B is the gene most significantly increased among 204 up-regulated genes (more than 2 fold over-expression) and Chemokine (C-C motif) ligand 20 is the gene most dramatically decreased among 491 down-regulated genes (more than 2 fold down-expression). The gene increased expression of Cxc110, Cyp11a1, Gadd45a, Gja1, Gpx2, Ifua4, Inpp5e, Sox4, and Stip1 are involved stress-response gene, and Cryab, Dnaja1, Hspa1a, Hspa8, Hspca, Hspcb, Hspd1, Hspd1, and Hsph1 are strongly associated with protein folding. Cell cycle associated genes (Bc13, Brca2, Ccnf, Cdk2, Ddit3, Dusp6, E2f1, Illa, and Junb) and inflammatory response associated genes (Cc12, Cc120, Cxc12, Il23a, Nos2, Nppb, Tgfb1, Tlr2, and Tnt) are down-regulated more than 2 times by geldanamycin treatment. We found that geldanamycin is related to expression of many genes associated with stress response, protein folding, cell cycle, and inflammation by DNA microarray analysis. Further experimental molecular studies will be needed to figure out the exact biological function of various genes described above and the physiological change of neuronal cells by geldanamycin. The resulting data will give the one of the good clues for understanding of geldanamycin under molecular level in the neurons.

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Nitric Oxide Dependency in Inflammatory Response-related Gene Transcripts Expressed in Lipopolysaccharide-treated RAW 264.7 Cells

  • Pie, Jae-Eun;Yi, Hyeon-Gyu
    • Molecular & Cellular Toxicology
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    • 제5권4호
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    • pp.354-363
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    • 2009
  • Cytotoxic Nitric oxide (NO) overproduced by inducible NO Synthase (iNOS or NOS2), which was induced in inflammatory reactions and immune responses directly or indirectly affects the functions as host defense and can cause normal tissue damage. Microarray analysis was performed to identify gene profiles of both NO-dependent and -independent transcripts in RAW 264.7 macrophages that use selective NOS2 inhibitors aminoguanidine ($100\;{\mu}M$) and L-canavanine (1 mM). A total of 3,297 genes were identified that were up- or down-regulated significantly over 2-fold in lipopolysaccharide (LPS)-treated macrophages. NO-dependency was determined in the expressed total gene profiles and also within inflammatory conditions-related functional categories. Out of all the gene profiles, 1711 genes affected NO-dependently and -independently in 567 genes. In the categories of inflammatory conditions, transcripts of 16 genes (Pomp, C8a, Ifih1, Irak1, Txnrd1, Ptafr, Scube1, Cd8a, Gpx4, Ltb, Fasl, Igk-V21-9, Vac14, Mbl1, C1r and Tlr6) and 29 geneas (IL-1beta, Mpa2l, IFN activated genes and Chemokine ligands) affected NO-dependently and -independently, respectively. This NO dependency can be applied to inflammatory reaction-related functional classifications, such as cell migration, chemotaxis, cytokine, Jak/STAT signaling pathway, and MAPK signaling pathway. Our results suggest that LPS-induced gene transcripts in inflammation or infection can be classified into physiological and toxic effects by their dependency on the NOS2-mediated NO release.

Changes in Antioxidant Enzyme Activities in the Gill And Digestive Glands of the Manila Clam Ruditapes philippinarum exposed to Cu

  • Min, Eun-Young;Jang, Suck-Woo;Kim, Sung-Gil;Kang, Ju-Cban
    • Fisheries and Aquatic Sciences
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    • 제13권1호
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    • pp.71-78
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    • 2010
  • We investigated the effect of Cu exposure on the activities of protective antioxidant enzymes in the gills and digestive glands of the manila clam Ruditapes phillippinarum exposed to subchronic concentrations (0, 20, 40, and $80{\mu}gL^{-1}$) of waterborne Cu. No mortality occurred during the experimental period, and no significant condition index differences were observed in any exposure group compared with the control. No significant differences were observed in the digestive glands and gills of the clams observed during 15 days of exposure, but after 30 days, the SOD activity in the gill showed a significant difference between the $80{\mu}gL^{-1}$ Cu-exposed group and the control. GPx activities in the digestive glands and gills were significantly lower after 30 days of Cu exposure. Gill GR activity in the high-exposure group ($80{\mu}gL^{-1}$) was significantly elevated compared with that in the control group. GST activities in the digestive glands of all groups did not change over 30 days. However, GST activity in the gill at $80{\mu}gL^{-1}$ Cu was significantly higher after 15 and 30 days of exposure. GSH activities in the gill showed patterns similar to those of GST activities during exposure periods. In the digestive glands, GSH activity was higher only at $80{\mu}gL^{-1}$ after 30 days exposure. In digestive glands and gills, the MDA levels of clams exposed to $80{\mu}gL^{-1}$ Cu were significantly higher after 30 days of exposure.

The Protective Effects of Acupuncture on Oxidative Stress Caused by Cadmium in the Kidney (카드뮴으로 유발된 산화적 스트레스에 대한 침 자극의 신장 보호 효과)

  • Shin, Hwa Young;Lee, Hyun Jong;Kim, Jae Soo
    • Journal of Acupuncture Research
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    • 제32권1호
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    • pp.1-11
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    • 2015
  • Objectives : This study was performed to inquire into the protective effects of acupuncture on oxidative stress caused by cadmium accumulation in the kidney. Methods : Sprague-Dawley male($150{\pm}30g$) rats were stabilized for 1 week and divided into 5 groups: normal, control, $LR_3$ acupuncture, $BL_{23}$ acupuncture and sham acupuncture. For three days experimental groups received oral doses of cadmium 2 mg/kg twice a day. Acupuncture was applied bilaterally at each point 10 times for two weeks. The depth of stimulation was 1 mm at right angles and torsion of acupuncture was produced 2 times per second for 1 minute. The kidneys were extracted and weighed after two weeks, and renal function was confirmed through blood urea nitrogen(BUN). We measured reactive oxygen species of the serum and kidney, and compared expression levels of superoxide dismutase(SOD), catalase, glutathione peroxidase(Gpx), nuclear factor erythroid derived 2-related factor 2(Nrf-2), heme oxygenase-1(HO-1), nuclear factor-${\kappa}B$(NF-${\kappa}B)$, cyclooxygenase-2(COX-2), inducible nitric oxide synthase (iNOS), Bax and Cytochrome c. Results : The $LR_3$ acupuncture group and $BL_{23}$ acupuncture group experienced significantly increased kidney weight, and decreased BUN compared to control group. In terms of oxidative stress, the $LR_3$ acupuncture group and $BL_{23}$ acupuncture group experienced significantly reduced reactive oxygen species compared to the control group. Conclusions : The $LR_3$ acupuncture group and $BL_{23}$ acupuncture group experienced showed the effects of antioxidant, anti-inflammatory and apoptosis protection. The $BL_{23}$ acupuncture group was more effective than $LR_3$ acupuncture group.

Effects of Bupleurum falcatum Extract on the Survival of Cancered ICR Mouse and the Growth of Cancer Cells such as J774A.1 Cells and L1210 Cells (시호추출물의 ICR 발암생쥐의 생존율 및 J774A.1 세포와 L1210 세포의 증식에 미치는 영향)

  • Ha, Kye-Kyung;Jung, Dae-Young;Park, Sie-Won
    • Korean Journal of Pharmacognosy
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    • 제35권4호통권139호
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    • pp.293-299
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    • 2004
  • The current investigation was carried out to find out the anticancer activity of the methanol extract from Buplerum falcatum against cancered ICR mouse and cancer cell lines such as J774A.1 and L1210 cells. Extract of Buplerum falcatum displayed the considerable augmentation(134%) of the survival of ICR mouse bearing Sarcoma 180 cancer. In addition, the cytotoxic effects of methanol extract of Buplerum falcatum against J774A.1 cells and L1210 cells were found to show $IC_{50}$ values of $57.3\;{\mu}g/ml$ and $54.6\;{\mu}g/ml$, respectively. In contrast to such cytotoxicity against cancer cells, the extract exerted only meagre toxicity against normal lymphocytes. The increased generation of $O_2^-$ and the considerably increased activities of super-oxide dismutase(SOD) and glutathione peroxidase(GPx) of both J774A.1 cells and L1210 cells in the presence of Buplerum falcatum extract implied that the observed cytotoxicities may have resulted from the detrimental effect of reactive oxygen species(ROS) evoked by Buplerum falcatum extract on the cancer cells.

The Anti-obesity Effects of Younggyechulgam-tang-ga Hwanggi on Obesity in Mice Induced by High Fat Diet (고지방식이 유도 비만생쥐에 대한 영계출감탕(苓桂朮甘湯) 가(加) 황기(黃芪)의 항비만 효과)

  • Jeong, Man-Jin;Woo, Chang-Hoon;Ahn, Hee-Duk
    • Journal of Korean Medicine Rehabilitation
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    • 제28권2호
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    • pp.1-20
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    • 2018
  • Objectives This study was conducted to experimentally evaluate the effects of Younggyechulgam-tang-ga Hwanggi(YGT) on obesity in mice induced by high fat diet. Methods The experiment was conducted with 4-week-old male mice divided into 5 groups. They were a normal diet group(Nor), a high fat diet group(Veh), a positive drug control group-orlistat 40 mg/kg(Oris), a 1.08 g/kg group(YGTL), and a 2.16 g/kg group(YGTH), and were tested for five weeks. Changes in antioxidant activity, body weight, organ weight, ROS, AST, ALT, TC, TG, HDL-C, LDL-C and lipid metabolism protein were checked. Results YGTL and YGTH group significantly reduced body weight compared to Veh group. YGTH group significantly reduced visceral fat weights compared to Veh group. In blood biochemistry analysis, ROS, AST, ALT, TC, TG and LDL-C in YGTL and YGTH group were significantly lower than Veh group. HDL-C increased significance in YGTL and YGTH group. In antioxidation protein analysis, Catalase, GPx and HO-1 have increased significantly in YGTL and YGTH group. YGTH group have increased $PPAR-{\alpha}$, p-AMPK compared to Veh group. but decreased FAS. SREBP-1, p-ACC levels in YGTL and YGTH group were decreased compared to Veh group, however CPT-1, UCP-2 levels in YGTL and YGTH group were increased compared to Veh group. Conclusions YGT has anti-obesity effects by regulating lipolysis and antioxidation in a diet-induced obesity model. Additional clinical studies are needed.

Early Gene Expression in Mouse Spleen Cells after Exposure to Nickel Acetate

  • Koh Jae-Ki;Kim Woo-Hyoung;Lee Chang-Ho;Nam Hae-Seon;Kim Sung-Ho;Woo Kee-Min;Lee Sang-Han
    • Toxicological Research
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    • 제22권2호
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    • pp.95-102
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    • 2006
  • Exposure to soluble nickel compound produces toxic effects on immune system, but the mechanism of action remains to be elucidated. Differential gene expression was studied to understand the potential molecular mechanism responsible for acute toxicity induced by nickel acetate in spleen cells. We exposed mouse spleen cells to nickel acetate with a nontoxic dose ($40{\mu}M$) and then extracted total RNA at 6 h and 12 h after exposure. The RNA was hybridized onto 10K mouse oligonucleotide microarrays, and data were analyzed using GeneSpring 7.1. Nickel had a modest effects on expression of many genes, in the range of 1.3-3 fold. The expression profile showed time-dependent changes in expression levels of differentially expressed genes, including some important genes related to cell cycle, apoptosis and DNA repair. In hierarchical cluster analysis of duplicate experiments, 111 genes were screened out. Out of these, 44 genes showing time- dependent up-regulation (>1.5 fold) and 38 genes showing down-regulation (>1.5 fold) at all time points were chosen for further analysis. The change in the expression of three genes (GPX1, GADD45B and FAIM) after nickel treatment was validated using RT-PCR. As a rule, a number of genes appear to be coordinately regulated between cell survival and cell death from nickel toxicity. In conclusion, changes in the gene profile in the spleen after nickel treatment are complex and genes with diverse functions are modulated. These findings will be contributed to the understanding of the complicated biological effects of nickel.

UVB Protective Effect of Yeast Originated Selenium Peptide on Fibroblast (효모 유래 셀레늄 펩타이드의 인간 섬유아세포에 대한 UVB 보호효과)

  • Lee, Hyang-Bok;Lee, Jung-Ok;Nguyen, Dung H.;Yoon, Sun-A;Um, Ji-Min;Lee, Yu-Ri;Moon, Hyung-In;Chung, Jin-Ho;Kim, Eun-Ki
    • KSBB Journal
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    • 제24권5호
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    • pp.463-468
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    • 2009
  • Selenium-containing peptide (Selenium peptide) was produced by autolysis of Saccharomyces cerevisiae which was cultured in inorganic selenium-supplemented medium. Selenium peptide showed antioxidant activity and protective effects on UVB irradiated human fibroblast. Minimal toxicity of selenium peptide was observed whereas selenium nitrate exhibited cell toxicity as low as $10^{-9}\;M$. Selenium peptide also increased human fibroblast growth, procollagen type I and also decreased MMP-1 (matrix metalloprotease-1). This result showed the potential of selenium peptide as a nontoxic antioxidant.

Remedy effects of dandelion and milk thistle on fatty liver hemorrhagic syndrome in laying hens

  • Young-Joon Cho;Jeong-Ran Min;Jeong-Hee Han;Sang-Hee Jeong
    • Korean Journal of Veterinary Service
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    • 제46권1호
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    • pp.1-13
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    • 2023
  • Fatty liver hemorrhagic syndrome (FLHS) is a metabolic disorder found in caged layer hens and causes reduced egg production and sudden death. Dandelion (Taraxacum coreanum, TC) and milk thistle (Cirsium japonicum var. ussuriense, CJ) are well known wild herbs inhabiting Korean peninsula and presenting antioxidative effects. This study investigated alleviate effects of these herbal mixture (6:4, w/w) composed of dried powder of TC and CJ against fatty liver in laying hens. The herbs mixture 5.0, 10.0, 20.0 or 40.0 g/kg feed was provided via feed admixture for 3 weeks to laying hens having FLHS. FLHS was induced by intramuscular injection of β-estradiol (2 mg/kg bw) 2 times per week for 3 weeks and supply with high caloric feed. Egg production rate was reduced from 76.2% at pre-treatment to 49.4% at 1 week and further decreased according to β-estradiol treatment. Increment of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (T-Chol) and total bilirubin (T-Bil) and decrement of serum superoxide dismutase (SOD) and glutathione peroxidase (GPX) with fatty liver were found by the treatment of β-estradiol. Supplementation of TC and CJ mixture via feed admixture recovered the reduction of egg production and attenuated serological changes and gross and pathological lesions of fatty liver with the best amelioration effects at 5 and 10 g TC and CJ mixture per kg feed. In conclusion, TC and CJ mixture attenuates FLHS by means of antioxidative effects. Further mechanistic study is required to explain TC and CJ's amelioration effects against FLHS in laying hens.