• Title/Summary/Keyword: GST M1

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The Effects of Gamisipjeon-tang on the Skin Regeneration of Deep Second Degree Burns in Mice

  • Yu, Hyun-Jung;Hong, Seung-Ug
    • The Journal of Korean Medicine
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    • v.31 no.3
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    • pp.107-121
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    • 2010
  • Objective: This study aimed to ascertain the curative effects of Gamisipjeon-tang (GST) used for wound healing on the skin regeneration of deep second degree burns in mice. Material & Methods: In vitro, the $I{\kappa}B$ kinase (IKK) mRNA expression, inducible nitric oxide synthase (iNOS) mRNA expression, and cyclooxygenase-2 (COX-2) mRNA expression in the GST concentration from 1 mg/$m{\ell}$ to 10 mg/$m{\ell}$ were measured. In vivo, the mice were divided into four groups : the normal group, the BE group (burn-elicited group, control group), the DC group (Duoderm CGF-treated group after burn elicitation), and the GST group (Gamisipjeon-tang treated group after burn elicitation). To determine the anti-inflammatory effects, nuclear factor (NF)-${\kappa}B$ p65, iNOS, COX-2 positive reaction were measured by immunohistochemistry. To estimate the skin regenerative effects, change of burn area, 5-bromo-2'-deoxyuridine (BrdU), and fibroblast growth factor (FGF) positive reaction were analyzed. Results: In vitro, the iNOS, IKK, COX-2 mRNA expression decreased according to the increase of GST concentration. The significant decrease of COX-2, iNOS, NF-${\kappa}B$ positive reaction were the highest in the GST group, followed by the DC group and the BE group (p<0.05). The diameter of burn area was significantly decreased in the GST group as compared to that in the DC and BE group (p<0.05). The BrdU and FGF positive reaction increased more significantly in the GST group than in the DC group, and more significantly in the DC group than in the BE group on the 3rd and 7th day after burn (p<0.05). FGF positive reaction increased in the BE and DC group, whereas it decreased significantly in the GST group on the 14th day (p<0.05). The BrdU positive reaction increased in the BE group, whereas it decreased significantly in the DC and GST group on the 14th day (p<0.05). Conclusions: This study shows that GST could decrease the inflammatory response and accelerate the skin regeneration as compared to the duoderm CGF in mice with deep second degree burns.

Studies on Synthetic 1,2-Benzothiazine Anti-inflammatory Agents: Pharmacological Effect and the Expression of Xenobiotic-metabolizing Enzymes (1,2-Benzothiazine계열 새로운 항염진통제에 대한 약리작용 및 대사효소발현 유형의 연구)

  • 김상건;조주연;권순경;이은방
    • YAKHAK HOEJI
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    • v.44 no.4
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    • pp.300-307
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    • 2000
  • Expression of xenobiotic-metabolizing enzymes can be altered by xenobiotics, which represents changes in the production of reactive metabolic intermediates as well as toxicities in tissues. Metabolic intermediates derived from xenobiotics are considered to produce the reactive oxygen species including drug free radicals and hydroxyl free radicals, which would be ultimately responsible for drug-induced toxicities. The effects of 1,2-benzothiazine anti-inflammatory agents on the expression of xenobiotic-metabolizing enzymes including major cytochrome P450s, microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) were studied in the liver with the aim of providing the part of information on potential production of reactive metabolites and hepatotoxicity by the agents. The synthetic compounds 24, 36 and 39 exhibited anti-inflammatory effects in rats as assessed by the Randall-Selitto method. The anti-inflammatory effect was detected as early as at 30 min after gavaging the agents with the ED5O being noted at 80 mg/kg, which was comparable to that of ibuprofen. Treatment of rats with each compound (100 mg/kg, 3d) resulted in no significant induction in the immunochemically-detectable cytochromes P45O 1A1/2, P450 2B1/2, P45O 2 Cl1 and P45O 2El. Changes in the mEN expression were also minimal, as evidenced by both Western blot and Northern blot analyses. Hepatic GST expression was slightly increased by the agents: GST Ya protein and mRNA expression was ~1.5-fold increased after treatment with compounds 24 and 39, whereas GST Yb1/2 and Yc1/2 mRNA levels were elevated 2- to 3-fold. In summary the effects of the synthetic 1,2-benzothiazines on the expression of major P45O, mEH and G57 were not significant, providing evidence that metabolic activation of the agents, potential drug interaction and hepatotoxicity would be minimal.

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Modulation of antioxidant defense system in the brackish water flea Diaphanosoma celebensis exposed to bisphenol A (비스페놀 A에 대한 기수산 물벼룩의 항산화 시스템의 변화)

  • Yoo, Jewon;Cha, Jooseon;Kim, Hyeri;Pyo, Jinwoo;Lee, Young-Mi
    • Korean Journal of Environmental Biology
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    • v.37 no.1
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    • pp.72-81
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    • 2019
  • Bisphenol A (BPA), a representative endocrine disrupting chemicals, has adverse effects on growth, development and reproduction in aquatic organisms. The object of this study was to investigate the modulation of antioxidant enzyme-coding genes using quantitative real time RT-PCR (qRT-PCR), enzyme activity and total protein content, to understand oxidative stress responses after exposure to BPA for 48 h in brackish water flea Diaphanosoma celebensis. The BPA ($3mg\;L^{-1}$) significantly upregulated the expression of Cu/Zn-SOD, Mn-SOD, and catalase (CAT) mRNA. Three GST isoforms (GST-kappa, GST-mu, and GST-theta) mRNA levels significantly increased at the rate of $0.12mg\;L^{-1}$ of BPA. In particular, GST-mu showed the highest expression level, indicating its key role in antioxidant response to BPA. SOD activity was induced with a concentration-dependent manner, and total protein contents was reduced. These findings indicate that BPA can induce oxidative stress in this species, and these antioxidants may be involved in cellular protection against BPA exposure. This study will provide a better understanding of molecular mode of action of BPA toxicity in aquatic organisms.

Gene Expression of Enzymes Related to Glutathione Metabolism in Anticancer Drug-resistant L1210 Sublines (항암제 내성 L1210세포의 Glutathione 대사 관련효소 유전자의 발현 양상)

  • Kim, Seong-Yong;Kim, Jae-Ryong;Kim, Jung-Hye
    • Journal of Yeungnam Medical Science
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    • v.12 no.1
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    • pp.32-47
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    • 1995
  • Glutathione(GSH) has a very important role in detoxification of cells and is closely related to antitumor drug-resistance of cancer cells. In order to evaluate the importance of glutathione metabolism in the drug-resistant cancer cells, the concentration of celluar GSH and activities of ${\gamma}$-glutamylcysteine synthetase(GCS), ${\gamma}$-glutamyl transpeptidase (GGT) and glutathione S-transferases(GST) in the adriamycin, vincristine, or cisplatin resistant L1210 (L1210AdR, L1210VcR, or L1210Cis) sublines were measured. Expression and amplification of GCS, GGT, and GST-${\pi}$ genes were also observed in the parent Ll210 and the drug-resistant Ll210 sublines. The concentration of GSH was increased 5.34 fold in L1210Cis, 2.83 fold in L1210VcR, and 1.78 fold in L1210AdR, compared to L1210. The activities of GCS and GGT were increased in drug-resistant L1210 sublines. The GST activity was increased in L1210VcR and L1210Cis but decreased in L1210AdR compared to Ll210. Expression of GCS, GGT, and GST-${\pi}$ genes were increased in the resistant L1210 sublines compare to the parent L1210 in northern blot analyses. Overexpression of GCS, GGT, and GST-${\pi}$ were observed in the resistant sublines, and the increases of the concentration of glutathione and the activities of GCS and GGT in the resistant sublines may be involved in a part of the drug-resistance in the resistant sublines.

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Nitrogen을 도핑시킨 Ge-Sb-Te 박막의 광전자 및 광흡수 분광학 연구

  • Sin, Hyeon-Jun;Jeong, Min-Cheol;Kim, Min-Gyu;Lee, Yeong-Mi;Kim, Gi-Hong;Jeong, Jae-Gwan;Song, Se-An;Sun, Zhimei
    • Proceedings of the Korean Vacuum Society Conference
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    • 2013.02a
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    • pp.186-186
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    • 2013
  • Nitrogen doped Ge-Sb-Te (N-GST) thin films for phase change random access memory (PRAM) applications were investigated by synchrotron-radiation-based x-ray photoelectron spectroscopy and absorption spectroscopy. Nitrogen doping in GST resulted in more favorable N atoms' bonding with Ge atoms rather than with Sb and Te atoms [1,2], which explains the higher phase change transition temperature than that of undoped Ge-Sb-Te thin film. Surprisingly, it was noticed that N atoms also existed in the form of molecular nitrogen, $N_2$, which is detrimental to the stability of the GST performance [3]. N-doped GST experimental features were also supported by ab-initio molecular dynamic calculations [2]. References [1] M.-C. Jung, Y. M. Lee, H.-D. Kim, M. G. Kim, and H. J. Shin, K. H. Kim, S. A. Song, H. S. Jeong, C. H. Ko, and M. Han, "Ge nitride formation in N-doped amorphous Ge2Sb2Te5", Appl. Phys. Lett. 91, 083514 (2007). [2] Zhimei Sun, Jian Zhou, Hyun-Joon Shin, Andreas Blomqvist, and Rajeev Ahuja, "Stable nitride complex and molecular nitrogen in N doped amorphous Ge2Sb2Te5", Appl. Phys. Lett. 93, 241908 (2008). [3] Kihong Kim, Ju-Chul Park, Jae-Gwan Chung, and Se Ahn Song, Min-Cherl Jung, Young Mi Lee, Hyun-Joon Shin, Bongjin Kuh, Yongho Ha, Jin-Seo Noh, "Observation of molecular nitrogen in N-doped Ge2Sb2Te5", Appl. Phys. Lett. 89, 243520 (2006).

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Cytoprotective Effect of Zinc-Mediated Antioxidant Gene Expression on Cortisol-Induced Cytotoxicity (Cortisol 유발 세포독성에 대한 아연 관련 항산화 유전자 발현 증가에 의한 세포보호 효과)

  • Chung, Mi Ja;Kim, Sung Hyun;Hwang, In Min
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.44 no.5
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    • pp.649-656
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    • 2015
  • The protective effect of zinc against cortisol-induced cell injury was examined in rainbow trout gill epithelial cells. Cells exposed to cortisol for 24 h showed increased leakage of lactate dehydrogenase (LDH) as well as decreased cell viability in a dose-dependent manner. Treatment with zinc ($100{\mu}M$ $ZnSO_4$) reduced the severity of both LDH release and cell death as well as protected cells against cortisol-induced caspase-3 activation, indicating reduction of apoptosis. Cortisol-induced cell death, leakage of LDH, and caspase-3 activation were blocked by the glucocorticoid receptor antagonist Mifepristone (RU-486), suggesting that cell injury was cortisol-dependent. In addition, we studied the effect of zinc on the expression of antioxidant genes such as metallothionein A (MTA), metallothionein B (MTB), glutathione-S-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD) during cortisol-induced cell injury. MTA, MTB, GST, and G6PD mRNA levels increased after treatment with zinc or cortisol, separately or in combination. Higher mRNA levels of MTA, MTB, GST, and G6PD were detected when cells were treated with $100{\mu}M$ $ZnSO_4$ and $1{\mu}M$ cortisol in combination at the same time compared to treatment with zinc or cortisol separately. Cells treated with zinc showed increased intracellular free zinc concentrations, and this response was significantly enhanced in cells treated with cortisol and zinc. In conclusion, zinc treatment inhibited cortisol-induced cytotoxicity and apoptosis through indirect antioxidant action.

Effect of Cadmium on the Expression of ABC Transporters and Glutathione S-transferase in the Marine Ciliate Euplotes crassus (카드뮴이 해양 섬모충(Euplotes crassus)의 ABC Transporters와 GST 유전자 발현에 미치는 영향에 관한 연구)

  • Kim, Hokyun;Kim, Se-Hun;Kim, Ji-Soo;Lee, Young-Mi
    • Journal of Marine Life Science
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    • v.1 no.2
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    • pp.79-87
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    • 2016
  • Heavy metals such as cadmium (Cd) are highly toxic to aquatic organisms and human, even at trace concentration. Herein we investigated the effect of Cd on the gene expression of ATP-binding cassette (ABC) transporters and glutathione S-transferase (GST) in marine ciliate Euplotes crassus. Seven ABC transporters and one GST genes were partially cloned and sequences, and thereafter, transcriptional modulation of these genes after exposure to Cd for 8 h was investigated using quantitative real time RT- PCR (qRT-PCR). As results, sequence analysis and phylogenetic study revealed that E. crassus ABCs are likely typical ABC transports, in particular, B/C family, and GST gene may be similar to GST theta isoform. A significant increase in the expression of ABCs, except for ABCB21 was observed in a concentration dependent manner after exposure to Cd (0.1 and 0.5 mg/l) for 8 h. The GST mRNA level was the highest at 0.5 mg/l Cd and then reduced until control level. These findings suggest that ABCs and GST may be involved in a protective mechanism against Cd-mediated toxicity in E. crassus.

Characterization of n-type In3Sb1Te2 and p-type Ge2Sb2Te5 Thin Films for Thermoelectric Generators (박막 열전 발전 소자를 위한 In3Sb1Te2와 Ge2Sb2Te5 박막의 열전 특성에 관한 연구)

  • Kang, So-Hyeon;Seo, Hye-Ji;Yoon, Soon-Gil
    • Korean Journal of Materials Research
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    • v.27 no.2
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    • pp.89-93
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    • 2017
  • A thin film thermoelectric generator that consisted of 5 p/n pairs was fabricated with $1{\mu}m$-thick n-type $In_3Sb_1Te_2$ and p-type $Ge_2Sb_2Te_5$ deposited via radio frequency magnetron sputtering. First, $1{\mu}m$-thick GST and IST thin films were deposited at $250^{\circ}C$ and room temperature, respectively, via radio-frequency sputtering; these films were annealed from 250 to $450^{\circ}C$ via rapid thermal annealing. The optimal power factor was found at an annealing temperature of $400^{\circ}C$ for 10 min. To demonstrate thermoelectric generation, we measured the output voltage and estimated the maximum power of the n-IST/p-GST generator by imposing a temperature difference between the hot and cold junctions. The maximum output voltage and the estimated maximum power of the $1{\mu}m$-thick n-IST/p-GST TE generators are approximately 17.1 mV and 5.1 nW at ${\Delta}T=12K$, respectively.

Site-directed Mutagenesis of Tyrosine 108 Residue in Human Glutathione S-Transferase P1-1

  • Ahn, So-Youn;Jeon, Sang-Hoon;Park, Hee-Joong;Kong, Kwang-Hoon
    • Bulletin of the Korean Chemical Society
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    • v.24 no.8
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    • pp.1188-1192
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    • 2003
  • In order to study the role of residue in the active site of glutathione S-transferase (GST), Tyr 108 residue in human GST P1-1 was replaced with alanine, phenylalanine and tryptophan by site-directed mutagenesis to obtain mutants Y108A, Y108F and Y108W. These three mutant enzymes were expressed in Escherichia coli and purified to electrophoretic homogeneity by affinity chromatography on immobilized GSH. The substitutions of Tyr108 significantly affected $K_m^{CDNB}$ and $K_m^{ETA}$, whereas scarcely affected $K_m^{GSH}$. The substitutions of Tyr108 also significantly affected $I_{50}$ of ETA, an electrophilic substrate-like compound. The effect of these substitutions on kinetic parameters and the response to inhibition suggests that tyrosine 108 in hGST P1-1 contributes to the binding of the electrophilic substrate and a major determinant in the binding of CDNB is the aromatic ring of Tyr108, not its hydroxyl group.

Lymphocyte DNA Damage and Anti-Oxidative Parameters are Affected by the Glutathione S-Transferase (GST) M1 and T1 Polymorphism and Smoking Status in Korean Young Adults (흡연 여부에 따른 Glutathione S-transferase (GST) M1 및 T1 유전자 다형성이 우리나라 젊은 성인의 임파구 DNA 손상과 항산화 영양상태 지표들 간의 관련성에 미치는 영향)

  • Han, Jeong-Hwa;Lee, Hye-Jin;Kang, Myung-Hee
    • Journal of Nutrition and Health
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    • v.44 no.5
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    • pp.366-377
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    • 2011
  • Glutathione S-transferase (GST) is a multigene family of phase II detoxifying enzymes that metabolize a wide range of exogenous and endogenous electrophilic compounds. GSTM1 and GSTT1 gene polymorphisms may account for inter-individual variability in coping with oxidative stress. We investigated the relationships between the level of lymphocyte DNA and antioxidative parameters and the effect on GST genotypes. GSTM1 and GSTT1 were characterized in 301 young healthy Korean adults and compared with oxidative stress parameters such as the level of lymphocyte DNA, plasma antioxidant vitamins, and erythrocyte antioxidant enzymes in smokers and non smokers. GST genotype, degree of DNA damage in lymphocytes, erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase (GSH-Px), and plasma concentrations of total radical-trapping antioxidant potential (TRAP), vitamin C, ${\alpha}$- and ${\gamma}$-tocopherol, ${\alpha}$- and ${\beta}$-carotene, and cryptoxanthin were analyzed. Lymphocyte DNA damage assessed by the comet assay was higher in smokers than that in non-smokers, but the levels of plasma vitamin C, ${\beta}$-carotene, TRAP, erythrocyte catalase, and GSH-Px were lower than those of non-smokers (p < 0.05). Lymphocyte DNA damage was higher in subjects with the GSTM1- or GSTT1-present genotype than those with the GSTM1-present or GSTT1- genotype. No difference in erythrocyte antioxidant enzyme activities, plasma TRAP, or vitamin levels was observed in subjects with the GSTM1 or GSTT1 genotypes, except ${\beta}$-carotene. Significant negative correlations were observed between lymphocyte DNA damage and plasma levels of TRAP and erythrocyte activities of catalase and GSH-Px after adjusting for smoking pack-years. Negative correlations were observed between plasma vitamin C and lymphocyte DNA damage only in individuals with the GSTM1-present or GSTT1- genotype. The interesting finding was the significant positive correlations between lymphocyte DNA damage and plasma levels of ${\alpha}$-carotene, ${\beta}$-carotene, and cryptoxanthin. In conclusion, the GSTM1- and GSTT1-present genotypes as well as smoking aggravated antioxidant status through lymphocyte DNA damage. This finding confirms that GST polymorphisms could be important determinants of antioxidant status in young smoking and non-smoking adults. Consequently, the protective effect of supplemental antioxidants on DNA damage in individuals carrying the GSTM1- or GSTT1-present genotypes might show significantly higher values than expected.