• Title/Summary/Keyword: S-transferase

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Human Glutathione S-Transferase P1 Suppresses MEKK1-mediated Apoptosis by Regulating MEKK1 Kinase Activity in HEK293 Cells

  • Zhao, Xin;Fan, Yumei;Shen, Jiayin;Wu, Yifan;Yin, Zhimin
    • Molecules and Cells
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    • v.21 no.3
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    • pp.395-400
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    • 2006
  • Glutathione S-transferase P1 (GSTP1) plays an important role in detoxification and the metabolism of xenobiotics. Here we show that GSTP1 also regulates the MEKK1-MKK7 signaling pathway. Over-expression of GSTP1 in HEK293 cells inhibited both ${\Delta}MEKK1$- and etoposide-induced apoptosis, and inhibited procaspase-3 activation and PARP cleavage. MEKK1- induced apoptosis requires both its kinase activity and proteolytic cleavage. ${\Delta}MEKK1$ activity was inhibited by over-expression of GSTP1 in vivo and MEKK1 kinase activity was also inhibited by GSTP1 in vitro when assayed with bacterially-expressed MKK7(KM) protein as substrate. GSTP1 inhibition of etoposide-induced cell apoptosis was mainly due to its ability to suppress MEKK1 kinase activity. The glutathione-conjugating activity of GSTP1 was essential for the above effects. These findings provide insight into the mechanism by which GSTP1 protects cells from genotoxin-induced apoptosis.

Theobroxide Treatment Inhibits Wild Fire Disease Occurrence in Nicotiana benthamiana by the Overexpression of Defense-related Genes

  • Ahn, Soon Young;Baek, Kwang-Hyun;Moon, Yong Sun;Yun, Hae Keun
    • The Plant Pathology Journal
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    • v.29 no.1
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    • pp.110-115
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    • 2013
  • Theobroxide, a novel compound isolated from a fungus Lasiodiplodia theobromae, stimulates potato tuber formation and induces flowering of morning glory by initiating the jasmonic acid synthesis pathway. To elucidate the effect of theobroxide on pathogen resistance in plants, Nicotiana benthamiana plants treated with theobroxide were immediately infiltrated with Pseudomonas syringae pv. tabaci. Exogenous application of theobroxide inhibited development of lesion symptoms, and growth of the bacterial cells was significantly retarded. Semiquantitative RT-PCRs using the primers of 18 defense-related genes were performed to investigate the molecular mechanisms of resistance. Among the genes, the theobroxide treatment increased the expression of patho-genesis-related protein 1a (PR1a), pathogenesis-related protein 1b (PR1b), glutathione S-transferase (GST), allen oxide cyclase (AOC), and lipoxyganase (LOX). All these data strongly indicate that theobroxide treatment inhibits disease development by faster induction of defense responses, which can be possible by the induction of defense-related genes including PR1a, PR1b, and GST triggered by the elevated jasmonic acid.

Effect of Prunella vulgaris L. on Chemopreventive Enzymes of Colorectal Cancer (꿀풀하고초가 직장암 예방효소 활성에 미치는 영향)

  • Shon, Yun-Hee;Seo, Jae-Beom;Nam, Kyung-Soo
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.22 no.1
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    • pp.126-130
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    • 2008
  • Water extract from Prunella vulgaris L. (PVW) was tested for colon cancer chemopreventive activity by measuring the activities of cytochrome P450 1A1, phase Ⅱ detoxification enzyme [quinone reductase (QR) and glutathione S-transferase (GST)] and ornithine decarboxylase (ODC) and glutathione (GSH) levels in cultured human colorectal adenocarcinoma HT-29 cells. PVW significantly inhibited 7,12-dimethylbenz[a]anthracene (DMBA)-induced cytochrome P450 1A1 activity at 10 and 50 ${\mu}g/ml$. PVW induced QR activity in a dose-dependent manner over a concentration range of $1{\sim}50\;{\mu}g/ml$. GST activity was also induced with the treatment of PVW in HT-29 cells. In addition GSH levels were increased with PVW. PVW inhibited ODC activity, a key enzyme of polyamine biosynthesis, which is enhanced in tumor promotion. These results suggest that Prunella vulgaris L. has colon cancer chemopreventive activity by inhibiting cytochrome P450 1A1 and ODC activities and by increasing phase Ⅱ enzyme activity and GSH levels.

The effect of caffeine on promotion step of diethylnitrosamine-initiated hepatic altered foci in a mid-term induction system (Caffeine이 diethylnitrosame에 의해 유도되는 preneoplastic hepatic altered foci 형성의 promotion 단계에 미치는 효과)

  • Kim, Sung-ho;Lee, Cha-soo
    • Korean Journal of Veterinary Research
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    • v.32 no.4
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    • pp.629-633
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    • 1992
  • Caffeine이 랫드의 간조직에서 diethylnitrosamine(200mg/kg B.W., DEN)에 의해 유도되는 preneoplastic altered foci형성의 promotion단계에 미치는 효과를 관찰한 바 다음과 같은 결과를 얻었다. Altered foci의 지표로 사용되는 glutathione S-transferase(GST-P)-positive foci의 수는 caffeine 음수 $m{\ell}$당 2mg 병행투여군($3.10{\pm}2.74$) 및 1mg병행 투여군($5.86{\pm}2.83$) 모두에서 DEN 단독투여 대조군($11.55{\pm}5.82$)에 비하여 현저히 낮게 나타났으며 면적 또한 caffeine 2mg 병행투여군($0.13{\pm}0.11$), 1mg 병행투여군($0.21{\pm}0.12$)에서 DEN 단독투여 대조군($0.76{\pm}0.33$)에 비하여 유의성있는 낮은 수치가 관찰되었다. 간 세포배양에서 unscheduled DNA synthesis(UDS)는 DEN($250{\mu}g/m{\ell}$ of medium)단독처리군에 비하여 caffeine($200{\mu}g/m{\ell}$ of medium) 처리시 약 70% 감소하였다. 이러한 결과는 caffeine이 간암발생의 promotion단계에 작용하여 억제효과를 나타냄을 암시하며 이는 DNA회복의 억제와 관계됨을 알 수 있었다.

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Effects of Acori Graminei Rhizoma Aqua-acupunture Solution(AGRAS) on Induction of Cancer Chemopreventive Enzymes (석창포(石菖蒲) 약침액(藥鍼液)의 암(癌) 예방(豫防) 관련 효소 유도 효과)

  • Roh Dong-Il;Lim Jong-Kook
    • Korean Journal of Acupuncture
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    • v.19 no.2
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    • pp.51-56
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    • 2002
  • Induction of phase II enzymes such as quinone reductase (QR) and glutathione S-transferase (GST) is considered a major mechanism of protection against initiation of carcinogenesis. The present study was performed to evaluate the chemopreventive activity of Acori Graminei Rhizoma aqua-acupuncture solution (AGRAS) and Acori Graminei Rhizoma water-extracted solution (AGRWS) by measuring the induction of phase II enzymes. AGRAS and AGRWS are potent inducers of quinone reductase activity in murine hepatoma Hepa1c1c7 cells. The levels of GSH and GST was increased sightly with AGRAS and AGRWS. These results suggest that AGRAS and AGRWS may act as blocking agents against carcinogenesis by induction of phase II enzymes.

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The effect of caffeine on initiation step of diethylnitrosamine-initiated hepatic altered foci in a mid-term induction system (Caffeine이 diethylnitrosamine에 의해 유도되는 preneoplastic hepatic altered foci 형성의 initiation 단계에 미치는 효과)

  • Kim, Sung-ho;Lee, Cha-soo
    • Korean Journal of Veterinary Research
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    • v.31 no.3
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    • pp.337-342
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    • 1991
  • Caffeine이 랫트의 간조직에서 diethylnitrosamine(200mg/kg B.W., DEN)에 의해 유도되는 preneoplastic altered foci형성의 initiation단계에 미치는 효과를 관찰한 바 다음과 같은 결과를 얻었다. Altered foci의 지표로 사용되는 glutathione S-transferase(GST-P)-positive foci의 수는 caffeine 음수수 ml 당 2mg병행투여군 $(7.48{\pm}3.33)$ 및 1mg 병행 투여군 $(7.50{\pm}3.32)$ 모두에서 DEN 단독투여대조군$(14.08{\pm}5.16)$에 비하여 현저히 낮게 나타났으며, 면적 또한 caffeine 2mg병행투여군 $(0.29{\pm}0.17)$, 1mg병행투여군 $(0.30{\pm}0.13)$에서 DEN단독투여대조군 $(0.46{\pm}0.21)$에 비하여 유의성 있는 낮은 수치가 관찰되었다. 이러한 결과는 caffeine이 간암발생의 initiation 단계에 작용하여 억제효과를 나타냄을 암시하였다.

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Induction of Quinone Reductase and Glutathione S-Transferase in Murine Hepatoma Cells by Flavonoid Glycosides

  • Kim, Jung-Hyun;Lee, Jeong-Soon;Kim, Young-Chan;Chung, Shin-Kyo;Kwon, Chong-Suk;Kim, Young-Kyoon;Kim, Jong-Sang
    • Preventive Nutrition and Food Science
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    • v.8 no.4
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    • pp.365-371
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    • 2003
  • The potential of seven flavonoid glycosides to induce quinone reductase (QR), an anticarcinogenic marker enzyme, in murine hepatoma cells (hepalc1c7) and its mutant cells (BPRc1) was evaluated. Among test compounds, kaempferol-3-O-glucoside, luteolin-6-c-glucoside, and quercetin-3-O-glucoside (Q-3-G) induced QR in hepalc1c7 cells in a dose-dependent manner. However, in BPRc1 cells lacking arylhydrocarbon receptor nuclear translocator (ARNT), only Q-3-G caused a significant induction of quinone reductase at the concentration range of 0.5 to 8 ug/mL, suggesting that it is a monofunctional inducer. Q-3-G induced not only phase 2 enzymes, including QR and glutathione-S-transferase, but also nitroblue tetrazolium reduction activity in HL-60 cells, a biochemical marker for cell differentiation promoting agents. In conclusion, Q-3-G merits further study to evaluate its cancer chemopreventive potential.

Responses of Renal Mixed Function Oxidase System in Rockfish (Sebastes schlegeli) Administered with 4-Nonylphenol (노닐페놀을 주사한 조피볼락의 신장 MFO (mixed function oxidase)의 반응)

  • JEON Joong-Kyun;LEE Ji-Seon;SOHN Young-Chang;HONG Gyong-Pyo;SHIM Won Joon;KIM Pyong-Kih;HAN Chang-Hee
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.36 no.6
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    • pp.573-577
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    • 2003
  • Effects of 4-nonylphenol (4-NP) on mixed function oxygenase (MFO) in the kidneies of rockfish (Sebastes schlegeli) were investigated. The cytochrome P45O (CYP) contents and NADPH cytochrome P450 reductase, NADH cytochrome b5 reductase and 7-ethoxyredorufin-O-deethylase (EROD) activities of microsome, glutathione S-transferase (GST) activity of cytosol in rockfish exposed to 4-NP for 7 days using an intraperitoneal injection (25 mg/kg) were quantitatively determined. The GST activity of rockfish exposed to 4-NP were higher, up to 5.2 times higher, than those in the control fish. The activities of NADPH-and NADH-dependent reductases were inhibited. On the other hand, CYP contents and EROD activity of the 4-NP exposed fish demonstrated neither an increasing or decreasing trend.

Age-associated Alteration in the Hapatic Superoxide Generation and Antioxidant Activities in the Senescence-accelerated Mice (노화촉진 생쥐에서 노화에 따른 활성산소 생성 및 항산화능의 변화)

  • Chung, Hae-Young;Kim, Yun-Kyung
    • YAKHAK HOEJI
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    • v.36 no.5
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    • pp.460-468
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    • 1992
  • Several bichemical parameters related to free radicals were estimated in senile-prone (P) and resistant(R) strains of male senescence-accelerated mice(SAM) at 2, 5 and 11 months of age. The superoxide generation was increased with age in SAM-R/1 and SAM-P/2. Compared to SAM-R/1, more generation of superoxide was significantly noted in the SAM-P/2 liver. The activities of Cu/Zn-superoxide dismutase and catalase were decreased during aging and these activities in SAM-P/2 were significantly lower than in SAM-R/l liver. The activities of glutathione S-transferase were varied with aging, whereas SAM-P/2 showed lower levels compared to SAM-R/l. The gradual decreases of glutathione, protein bound-SH and nonprotein bound-SH contents were noted with increasing age. SAM-P/2 liver contained lesser amounts of glutathione and nonprotein bound-SH compared to SAM-R. In conclusion, superoxide generation was increased whereas the antioxidant enzyme activities were decreased during aging in SAM-R/1. In addition, SAM-P/2 strain showed more superoxide generation and less antioxidant enzyme activities than SAM-R/1 in the liver, thus we assume that these factors might accelerate the senescence of SAM-P/2 strain.

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