• 제목/요약/키워드: Glutathione conjugation

검색결과 45건 처리시간 0.029초

PULMONARY XENOBIOTIC CONJUGATION IN THE ISOLATED PURFUSED RABBIT LUNG AND IN VITRO: EFFECT OF ETHANOL

  • Yang, C.Mierha;Carlson, Gary P.
    • Toxicological Research
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    • 제7권2호
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    • pp.191-208
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    • 1991
  • Pulmonary conjugation pathways may be important for the metabolism of xenobiotics introduced via airways of systemically. The objective of this study was to determine the pulmonary conjugating capacity in both the isolated perfused rabbit lung (IPRL) and in vitro, and the ability of ethanol to alter the above. The IPRL was capable of conjugating glutathione (GSH) with either 1-chloro-2,4-dinitrobenzene (CDNB) of 1,2-epoxy-(p-nitrophenoxy) propane(ENP). The pulmonary GSH conjugation with ENP was inhibited by cibacron blue, indicating the presence of glutathione-S-transferase (GST) u and/or classes, but it was not altered by buthionine sulfoximine, a selective inhibitor of Gamma-glutamylcysteine synthetase.

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Chlorothalonil- Biotransformation by Glutathione S- Transferase of Escherichia coli

  • Kim, Young-Mog;Park, Kunbawui;Jung, Soon-Hyun;Park, Jun-Ho;Kim, Won-Chan;Joo, Gil-Jae;Rhee, In-Koo
    • Journal of Microbiology
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    • 제42권1호
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    • pp.42-46
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    • 2004
  • It has recently been reported that one of the most important factors of yeast resistance to the fungicide chlorothalonil is the glutathione contents and the catalytic efficiency of glutathione S-transferase (GST) (Shin et al., 2003). GST is known to catalyze the conjugation of glutathione to a wide variety of xenobiotics, resulting in detoxification. In an attempt to elucidate the relation between chlorothalonil-detoxification and GST, the GST of Escherichia coli was expressed and purified. The drug-hypersensitive E. coli KAM3 cells harboring a plasmid for the overexpression of the GST gene can grow in the presence of chlorothalonil. The purified GST showed chlorothalonil-biotransformation activity in the presence of glutathione. Thus, chlorothalonil is detoxified by the mechanism of glutathione conjugation catalyzed by GST.

제초제 Alachlor의 선택성에 관한 연구;I. 약해와 글루타치온 Conjugation 반응 (Studies on the Selectivity of Herbicide Alachlor;I. Phytotoxicity and Glutathione Conjugation)

  • 박창규;황을철
    • 한국환경농학회지
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    • 제6권1호
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    • pp.44-49
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    • 1987
  • 본 연구는 제초제인 alachlor이 가지는 선택성이 식물고유의 생화학적 차이에 기인한다는 가정하에, 이의 규명을 목적으로 수행하였다. 공시작물인 대두, 배추 및 피는 alachlor 수용액의 처리로 경중의 약해를 입었으며 그 피해는 해당식물의 glutathione 또는 homoglutathione 함량이 많을 수록 적었다. 비효소적 반응조건 하에서 가한 alachlor의 17.7%가 GS-alachlor conjugate로 전환됨을 관찰하였으며, 이어 수행한 공시작물의 유묘시험에서는 처리한 C-14 표지 alachlor이 단시간(24hrs)에 4∼5개의 수용성 대사물로 전환되 었으며, 주요대사물로 대두에서는 homoglutathione-alachlor, 깨, 배추 그리고 피에서는 glutathione-alachlor conjugates를 잠정적으로 확인하였다. 본 연구에서 채택한 3종의 공시식물의 경우, 식물체 내에서 glutathione (및 homoglutathione)과 alachlor와의 phase Ⅱreaction인 conjugation 반응이 해독반응으로 작용, alachlor의 선택성에 공헌하는 것으로 해석하였다.

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제초제 Alachlor 의 선택성에 관한 연구;II. 대사론적 접근 (Studies on the Selectivity of the Herbicide Alachlor;II. A Metabolic Approach to Selectivity)

  • 황을철;박창규
    • 한국환경농학회지
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    • 제13권2호
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    • pp.209-215
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    • 1994
  • Absorption, translocation, and metabolism of the herbicide alachlor in soybean, Chinese cabbage, and barnyard grass seedlings were examined and compared with each other using [phenyl-U-$^{14}C$] alachlor in search of a primary factor contributing to the selectivity of alachlor. When root of each seedling was immersed into the solution containing [$^{14}C$]alachlor, the amount of absorbed radioactivity/mg dry matter of seedling which was suggested to be correlated with the susceptibility of plants to alachlor decreased in the order of soybean ${\gg}$ Chinese cabbage ${\geq}$ barnyard grass and the rate of translocation to shoot was Chinese cabbage ${\geq}$ barnyard grass ${\gg}$ soybean. These orders did not consistently explain the selective phytotoxicity of alachlor. Analyses of extracts by reverse phase chromatography showed that alachlor was detoxified by conjugation with glutathione in all three plants and the rate of glutathione conjugation of soybean, the resistant species to alachlor, was the greatest, while that of barnyard grass, the susceptible, was the lowest among three plants. This result explained well the selective phytotoxicity of alachlor. Both absorption and translocation contribute undoubtedly to the selectivity by influencing the active internal concentration of alachlor. However, neither of them appeared to be a primary factor. It was concluded that the most important primary factor was the rate of glutathione conjugation, which detoxifies alachlor and plays an important role in selectivity.

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Changes in drug metabolism during hypoxia/reoxygenation in isolated perfused rat

  • Seo, Min-Young;Cho, Tai-Soon;Lee, Sun-Mee
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 1997년도 춘계학술대회
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    • pp.98-98
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    • 1997
  • This study was done to investigate the effect of vitamin E on hypoxia/reoxygenation-induced hepatic injury in isolated perfused rat liver. Rats were pretreated with vitamin E or vehicle(soybean oil). Isolated livers from fasted 18 hours were subjected to 45min of low flow hypoxia or N$_2$ hypoxia followed by reoxygenation for 30min. The perfusion medium used was KHBB(pH 7.4) and 50${\mu}$㏖/$\ell$ of ethoxycoumarin was added to the perfusate to determine the ability of hepatic drug-metabolizing systems, In low flow hypoxia model, total glutathione and oxidised glutathione levels were significantly increased by hepoxia/reoxygenation with slight increase in LDH levels. These increases were prevented by vitamin E pretreatment. In N$_2$ hypoxia model, LDH, total glutathione and oxidized glutathione levels were increased significantly by hypoxia but restored to normal level by reoxygenation. Vitamin E had little effect on this hypoxic damage. There were no significant changes in the rate of hepatic oxidation of 7-EC to 7-HC in both hepoxic models. But, the subsequent conjugation of 7-HC by sulfate or glucuronic acid were significantly decreased by hypoxia, but restored by reoxygenation in both hypoxia models. As opposed to our expectation, treatment with vitamin E aggrevated the decrease of the rate of conjugation and even inhibited the restoration by reoxygenation. Our findings suggest that hypoxia/reoxygenation diminishes phase II drug metabolizing function and this is, in part, related to decreased energy level.

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Hepatotoxic Effect of 1-Bromopropane and Its Conjugation with Glutathione in Male ICR Mice

  • Lee Sang Kyu;Jo Sang Wook;Jeon Tae Won;Jun In Hye;Jin Chun Hua;Kim Ghee Hwan;Lee Dong Ju;Kim Tae-Oh;Lee Eung-Seok;Jeong Tae Cheon
    • Archives of Pharmacal Research
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    • 제28권10호
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    • pp.1177-1182
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    • 2005
  • The hepatotoxic effects of 1-bromopropane (1-BP) and its conjugation with glutathione were investigated in male ICR mice. A single dose (1000 mg/kg, po) of 1-BP in corn oil to mice significantly increased serum activities of alanine aminotransferase and aspartate aminotransferase. Glutathione (GSH) content was dose-dependently reduced in liver homogenates 12 h after 1-BP treatment. In addition, 1-BP treatment dose-dependently increased levels of S-pro-pyl GSH conjugate at 12 h after treatment, as measured by liquid chromatography-electro-spray ionization tandem mass spectrometry. The GSH conjugate was maximally increased in liver at 6 h after 1-BP treatment (1000 mg/kg), with a parallel depletion of hepatic GSH content. Finally, 1-BP induced the production of malondialdehyde in liver. The present results suggest that 1-BP might cause hepatotoxicity, including lipid peroxidation via the depletion of GSH, due to the formation of GSH conjugates in male ICR mice.

Human glutathione S-transferase 중 tyrosine 7 잔기의 기능 분석 (Functional analysis of Tyr7 residue in human glutathione S-transferase P1-1)

  • 공광훈;박희중;윤석영;조성희
    • 분석과학
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    • 제10권5호
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    • pp.378-385
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    • 1997
  • 본 실험은 human glutathione S-transferase P1-1의 tyrosine 7 잔기에 대한 변이체를 작성하고, 기질특이성과 저해제의 효과를 조사하여, 이 잔기의 기능을 분석한 것이다. 1,2-dichloro-4-nitrobenzene과 1,2-epoxy-3-(p-nitrophenoxy)propane에 대한 GSH 포합반응에 대한 활성은 야생형에 비해 변이체 Y7F에서는 3~5%로 크게 저하하였으며, 효소에 결합한 GSH의 thiol기의 pKa는 2.4 pK 높았다. 저해제 hematin에 대한 $I^{50}$값은 야생형과 변이체 Y7F에서 비슷하게 나타났으며, 저해제 benastatin A와 S-(2,4-dinitrophenyl) glutathione에 대한 $I^{50}$값들은 다소 감소하였다. 이러한 결과들로부터 tyrosine 7 잔기는 기질의 결합에 관여하기보다 GSH-chloronitrobenzene 유도체와 GSH-epoxide 포함반응에 대한 촉매활성에 중요하다고 생각된다.

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율무(Coix lacryma-jobi)의 제초제 Simazine에 대한 내성기구 (Tolerance Mechanism to Simazine in Coix lacryma-jobi)

  • 마상용;김종석;전재철
    • 한국환경농학회지
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    • 제16권1호
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    • pp.37-43
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    • 1997
  • 율무의 simazine에 대한 내성이 GSH와의 conjugation에 의한 약제의 불활성화 반응에 기인하는지 여부를 검정하기 위하여 화본과 작물인 옥수수와 비교하여 약제의 흡수 및 대사속도, GSH 함량 및 GST 활성, GST isozyme의 발현 양상 및 작용점에서의 약제에 대한 감수성의 차이를 조사하였다. 율무와 옥수수 모두 배양액중에 포함된 simazine에 대하여 약제처리 초기부터 빠른 흡수를 보였으며, 처리 12시간 후에는 두 초종 간의 흡수속도에 있어서 차이가 인정되지 않았다. 율무에 흡수된 simazine은 GSH-simazine conjugate의 형태로 신속히 대사되었으며, 특히 약제처리 $1{\sim}6$시간 까지의 처리 초기에는 율무에서의 대사속도가 옥수수에 비하여 약 2배정도 빠르게 나타났다. 두 초종 모두 초엽부에서 가장 높은 GSH 함량 분포를 보였다. 초종별로는 율무에서의 GSH 함량이 옥수수에 비하여 전반적으로 높게 나타났으며, 특히 율무의 초엽부와 근부에서 옥수수에 비하여 GSH함량이 각각 1.5배와 2.3배씩 높게 나타났다. GST[CDNB] 활성은 초종 간에 차이가 인정되지 않았으나, GST[simazine] 활성에 있어서는 옥수수에 비하여 율무의 모든 조직에서 약 2배 정도 높은 활성을 보였다. 두 초종 모두 지상부에서의 GST[simazine]활성이 근부에 비하여 $20{\sim}30%$ 정도 높게 나타났다. 율무와 옥수수에서 나타난 simazine에 대하여 특이성을 갖는 GST 활성의 차이를 이해하기 위하여 FPLC-anion exchange 컬럼을 이용하여 GST isozyme 활성을 조사하였다. 율무에 있어서 GST[CDNB] 활성을 보이는 1개 피크와 GST[simazine] 활성을 보이는 2개의 피크가 옥수수의 활성 피크와 같은 NaCl 농도범위에서 나타났으며, 이들의 활성은 옥수수에 비하여 높게 나타났다. 옥수수에서는 나타나지 않은 1개의 GST[simazine] 활성 피크가 율무에서 검출되었으며, 이 GST[simazine] 활성은 CDNB에 대하여 전혀 활성을 나타내지 않았기 때문에 율무에 simazine 특이성의 다른 GST isozyme이 존재함을 시사해 주고 있다. 율무와 옥수수의 완전 엽으로부터 추출한 엽록체 thylakoid막에 의한 전자전달 활성은 simazine $1{\sim}100\;{\mu}M$ 수준에서 매우 유사한 경향으로 억제되었다. 이상의 결과들은 율무의 simazine 내성이 흡수된 약제가 GSH와의 conjugation에 의하여 신속히 불활성화됨으로써 나타나며, 이러한 simazine 대사활성의 차이는 식물체에 내재하는 GSH 함량 및 GST 활성과 밀접한 상관성이 있음을 시사해 주고 있다.

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BIOACTIVATION OF DIBROMOETHANE BY CONJUGATION WITH GLUTAHIONE

  • Kim, Dong-Hyun
    • Toxicological Research
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    • 제7권2호
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    • pp.231-238
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    • 1991
  • The pesticide and carcinogen ethylene dibromide(EDB) is metabolized both by cytosolic GSH S-transferase and by microsomal mixed function oxygenase. Cytochrome P-450 IIE1 appears to be major enzyme to metabolize EDB.EDB is activated to a mutagen by enzymatic conjugation with glutathione (GSH). Such activation is an exception to the general mode of detoxification via GSH S-transferase action. The primary DNA adduct (>95) is S-[2-(N7-guanyl)ethyl] GSH and a minor adduct is S-[2-(N7-guanyl)ethyl]cysteine, which is excreted in the urine and may serve as a biomarker of damage.

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Role of Glutathione Conjugation in 1-Bromobutane-induced Immunotoxicity in Mice

  • Lee, Sang-Kyu;Lee, Dong-Ju;Jeon, Tae-Won;Ko, Gyu-Sub;Yoo, Se-Hyun;Ha, Hyun-Woo;Kang, Mi-Jeong;Kang, Won-Ku;Kim, Sang-Kyum;Jeong, Tae-Cheon
    • Toxicological Research
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    • 제26권2호
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    • pp.101-108
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    • 2010
  • Halogenated organic compounds, such as 1-bromobutane (1-BB), have been used as cleaning agents, agents for chemical syntheses or extraction solvents in workplace. In the present study, immunotoxic effects of 1-BB and its conjugation with glutathione (GSH) were investigated in female BALB/c mice. Animals were treated orally with 1-BB at 375, 750 and 1500 mg/kg in corn oil once for dose response or treated orally with 1-BB at 1500 mg/kg for 6, 12, 24 and 48 hr for time course. S-Butyl GSH was identified in spleen by liquid chromatography-electrospray ionization tandem mass spectrometry. Splenic GSH levels were significantly reduced by single treatment with 1-BB. S-Butyl GSH conjugates were detected in spleen from 6 hr after treatment. Oral 1-BB significantly suppressed the antibody response to a T-dependent antigen and the production of splenic intracellular interlukin-2 in response to Con A. Our present results suggest that 1-BB could cause immunotoxicity as well as reduction of splenic GSH content, due to the formation of GSH conjugates in mice. The present results would be useful to understand molecular toxic mechanism of low molecular weight haloalkanes and to develop biological markers for exposure to haloalkanes.