• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.120.2-120.2
• /
• 2003

Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this is detoxification and metabolizing more than 50% clinical drugs in use. Expression of CYP3A4 is transciptionally regulated by the Pregnenolone X receptor (PXR), of which human form is Steroid and Xenobiotics receptor (SXR). SXR is activated by wide range of endogenous and exogenous compounds, and then induces CYP3A4 gene expression. In the previous study, it has been known that proximal promoter (-864 to +64) does not response to chemical inducers such as pregnenolone 16a-carbonitrile (PCN), Rifampicin, Estrogen in terms of transcription of CYP 3A4 in cultured cells. (omitted)

• Food Science and Biotechnology
• /
• v.17 no.3
• /
• pp.613-622
• /
• 2008

Cancer chemopreventive effects can be exerted through the induction of phase II detoxification enzymes and the inhibition of inflammatory responses. In this study, the cancer chemopreventive effects and anti-inflammatory responses of 30 seaweed extracts were examined. The extracts of Dictyota coriacea and Cutleria cylindrica exhibited the high chemoprevention index, having 4.36 and 4.66, respectively. They also activated antioxidant response element at $100\;{\mu}g/mL$ by about 3-fold while did not activate xenobiotic response element. Seven seaweed extracts, Ishige okamurae, Desmarestia ligulata, Desmarestia viridis, Dictyopteris divaricata, D. coriacea, Sargassum horneri, and Sargassum yezoense, showed significant inhibition on nitric oxide (NO) and prostaglandin $E_2$ ($PGE_2$) production in a dose-dependant manner in $5-20\;{\mu}g/mL$. These seaweed extracts could be used as food materials for cancer chemoprevention. D. coriacea could contain potential chemopreventive agents not only that regulate genes via an ARE-dependent mechanism but also prevent the inflammation through inhibition of NO and $PGE_2$ production.

• Korean Journal of Fisheries and Aquatic Sciences
• /
• v.43 no.5
• /
• pp.428-436
• /
• 2010

Sea-urchins (Anthocidaris crassispina) are widely distributed in the East Sea of Korea. The aim of this study was to evaluate the hepatoprotective effects of sea-urchin roe on bromobenzene (BB)-induced liver damage in rats. The antioxidative and detoxifying properties of sea-urchin roe in BB-poisoned rat liver was examined by chemical analysis of serum aminotransferase (AST, ALT), glutathione S-transferase (GST), $\gamma$-glutamylcystein synthetase, glutathione reductase, epoxide hydrolase, amino-N-demethylase (AD), aniline hydrolase (AH) enzyme activity, as well as lipid peroxide and glutathione contents. Sea-urchin roe inhibited the increase of serum AST, ALT enzyme activity. Increasing lipid peroxide contents and AD and AH activities were significantly decreased in ethanol extract of sea-urchin roe. GST, $\gamma$-glutamylcystein synthetase, glutathione reductase and epoxide hydrolase enzyme activities increased in sea-urchin roe-fed group, compared with the BB-treated group. These results suggest that sea-urchin roe facilitates recovery from liver damage by enhancing antioxidative defense mechanisms and hepatic detoxication metabolism.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.4
• /
• pp.2221-2224
• /
• 2013

The glutathione S-transferases (GSTs) are a family of enzymes involved in the detoxification of a wide range of chemicals, including important environmental carcinogens, as well as chemotherapeutic agents. In the present study 294 acute leukemia cases, comprising 152 of acute lymphocytic leukemia (ALL) and 142 of acute myeloid leukemia, and 251 control samples were analyzed for GSTM1 and GSTT1 polymorphisms through multiplex PCR methods. Significantly increased frequencies of GSTM1 null genotype (M0), GSTT1 null genotype (T0) and GST double null genotype (T0M0) were observed in the both ALL and AML cases as compared to controls. When data were analyzed with respect to clinical variables, increased mean levels of WBC, Blast %, LDH and significant reduction in DFS were observed in both ALL and AML cases with T0 genotype. In conclusion, absence of both GST M & GST T might confer increased risk of developing ALL or AML. The absence of GST enzyme might lead to oxidative stress and subsequent DNA damage resulting in genomic instability, a hallmark of acute leukemia. The GST enzyme deficiency might also exert impact on clinical prognosis leading to poorer DFS. Hence GST genotyping can be made mandatory in management of acute leukemia so that more aggressive therapy such as allogenic stem cell transplantation may be planned in the case of patients with a null genotype.

• Journal of Haehwa Medicine
• /
• v.8 no.1
• /
• pp.711-726
• /
• 1999

Aging in the life form occurs due to a gradual progression of the body growth and degeneration. Morphological and functional changes in the body decreases the adaptation and prevention capacity leading into the decline of a life force. Various studies have been released to examine the anti-aging effects of herbal prescriptions. This experiment has chosen Boganhwan which is used for the deficiency of the liver function and studied the anti-aging factors by examining the biotransformation enzymes. The following results were obtained in this study: 1. Hepatic lipid peroxide activity was significantly suppressed in the experimental group treated with Boganhwan for 2 weeks at the dosage of 350mg/kg, while other dosage groups did not present much changes. 2. Insignificant changes were shown for the cytochrome P-450 level, aminopyrine demethylase, and aniline hydroxylase (AH) activities. Cytochrome P-450 do not appears to be a part of the detoxification scheme. 3. Boganhwan decoction treated group showed most significant increase of superoxide dismutase (SOD), catalase, superoxide, and glutathione activities at the concentration of 350mg/kg and 500mg/kg. 4. Glutathione S-transferase and glutathione made most significant increase at the decoction concentration of 350mg/kg and 500mg/kg compared to the control group. 5. Hepatic glutathione concentration, protein bound-SH, and nonprotein bound-SH made most significant increase at the decoction concentration of 350mg/kg and 500mg/kg compared to the control group. From the above results, Boganhwan decoction played an important role in eliminating foreign substances in the body excluding cytochrome P-450 enzyme system. Thus, Boganhwan decoction can provide substantial aid in preventing and treating senile related illnesses.

• Molecules and Cells
• /
• v.28 no.5
• /
• pp.479-487
• /
• 2009

Glutathione reductase (GR) is an enzyme that recycles a key cellular antioxidant molecule glutathione (GSH) from its oxidized form (GSSG) thus maintaining cellular redox homeostasis. A recombinant plasmid to overexpress a GR of Brassica rapa subsp. pekinensis (BrGR) in E. coli BL21 (DE3) was constructed using an expression vector pKM260. Expression of the introduced gene was confirmed by semi-quantitative RT-PCR, immunoblotting and enzyme assays. Purification of the BrGR protein was performed by IMAC method and indicated that the BrGR was a dimmer. The BrGR required NADPH as a cofactor and specific activity was approximately 458 U. The BrGR-expressing E. coli cells showed increased GR activity and tolerance to $H_2O_2$, menadione, and heavy metal ($CdCl_2$, $ZnCl_2$ and $AlCl_2$)-mediated growth inhibition. The ectopic expression of BrGR provoked the co-regulation of a variety of antioxidant enzymes including catalase, superoxide dismutase, glutathione peroxidase, and glucose-6-phosphate dehydrogenase. Consequently, the transformed cells showed decreased hydroperoxide levels when exposed to stressful conditions. A proteomic analysis demonstrated the higher level of induction of proteins involved in glycolysis, detoxification/oxidative stress response, protein folding, transport/binding proteins, cell envelope/porins, and protein translation and modification when exposed to $H_2O_2$ stress. Taken together, these results indicate that the plant GR protein is functional in a cooperative way in the E. coli system to protect cells against oxidative stress.

• The Journal of Korean Medicine
• /
• v.25 no.4
• /
• pp.36-42
• /
• 2004

Objective : Glutathione S-transferase polymorphism (GST) were examined in 120 cases with ischemic cerebrovascular disease (ICVD) to test the hyperthesis that GST polymorphisms confer a risk to an individual to develop ICVD. Tobacco smoking is a major cause of both cancer and vascular disease. Methods : therefore We were stratified the subjects with ICVD for smoking status, and then examined whether polymorphisms in this detoxification enzyme gene, GST, influence risk of ICVD Results : Neither GSTM1 nor GSTT1 genotypes in the ICVD group was significantly different from the control group (n=207), even in smokers. We attempted the combined analyses for GSTM1 and GSTT1 genotypes in ICVD for smoking status. No significant association observed between the combined genotypes and ICVD Conclusion : Our observation do not confirm the effect of the GSTM1 and GSTT1 genotypes as a risk factor for ICVD, even in smokers.

• Korean Journal of Environmental Biology
• /
• v.24 no.2 s.62
• /
• pp.195-200
• /
• 2006

The response of hepatic mixed function oxygenase (MFO) system was investigated in olive flounder exposed to formalin. Hepatic microsome of olive flounder incubated in vitro with formalin demonstrated the induction of cytochrome P450 (CYP), ethoxyresorufin deethylase (EROD), cytochrome P450 reductase (P450R) and cytochrome b5 reductase (b5R) activity. In addition, olive flounder was exposed to 100, 300 and 500 ppm of formalin for 1 h and then transferred to a flow-through type of 1000 L aquarium. Hepatic MFO enzyme activity was determined for 72 h. As the result, hepatic CYP, P450R and EROD activities increased following exposure of formalin, but b5R and GST showed no significant change. These results imply that CYP and P450R can be considered as main hepatic enzymes involving in detoxification of formalin.

• BMB Reports
• /
• v.48 no.11
• /
• pp.609-617
• /
• 2015

NAD(P)H:quinone oxidoreductase (NQO1), an obligatory two-electron reductase, is a ubiquitous cytosolic enzyme that catalyzes the reduction of quinone substrates. The NQO1- mediated two-electron reduction of quinones can be either chemoprotection/detoxification or a chemotherapeutic response, depending on the target quinones. When toxic quinones are reduced by NQO1, they are conjugated with glutathione or glucuronic acid and excreted from the cells. Based on this protective effect of NQO1, the use of dietary compounds to induce the expression of NQO1 has emerged as a promising strategy for cancer prevention. On the other hand, NQO1-mediated two-electron reduction converts certain quinone compounds (such as mitomycin C, E09, RH1 and β-lapachone) to cytotoxic agents, leading to cell death. It has been known that NQO1 is expressed at high levels in numerous human cancers, including breast, colon, cervix, lung, and pancreas, as compared with normal tissues. This implies that tumors can be preferentially damaged relative to normal tissue by cytotoxic quinone drugs. Importantly, NQO1 has been shown to stabilize many proteins, including p53 and p33ING1b, by inhibiting their proteasomal degradation. This review will summarize the biological roles of NQO1 in cancer, with emphasis on recent findings and the potential of NQO1 as a therapeutic target for the cancer therapy.

• Proceedings of the Korean Society of Applied Pharmacology
• /
• 2003.11a
• /
• pp.88-88
• /
• 2003

Cytochrome P-450 3A4 (CYP3A4) is major enzyme in human liver, the role of this is detoxification and metabolizing more than 50% clinical drugs in use. Expression of CYP3A4 is transciptionally regulated by the Pregnenolone X receptor (PXR), of which human form is Steroid and Xenobiotics receptor (SXR). SXR is activated by wide range of endogenous and exogenous compounds, and then induces CYP3A4 gene expression. In the previous study, it has been known that proximal promoter (-864 to +64) does not response to chemical inducers such as pregnenolone 16a-carbonitrile (PCN), Rifampicin, Estrogen in terms of transcription of CYP 3A4 in cultured cells. Here, we developed luciferase reporter gene assay system to detect SXR-based CYP 3A4 transcriptional activity. We have used CYP3A4-Luc plasmid that contains proximal promoter of human CYP3A4 gene upstream of the luciferase gene. We did transient transfection of 3A4-luciferase gene and SXR. In the HepG2 cells transfected with CYP3A4-Luc, when rifampicin treatment was combined with histone deacetylase inhibitor (HDAC Inhibitor), such as Trichostatin A, Hc-toxin and IN 2001 of the luciferase activity was induced 10-20 fold over control.