• Proceedings of the Korean Society of Toxicology Conference
• /
• 2002.05a
• /
• pp.24-42
• /
• 2002

Antioxidant responsive element (ARE) mediates the transcriptional activation of the genes encoding phase II drug metabolizing enzymes and antioxidative stress genes. The ARE consensus sequence shows high similarity to NF-E2 binding sequence, a cisacting erythroid gene regulatory element.(omitted)

• Toxicological Research
• /
• v.17
• /
• pp.299-304
• /
• 2001

Xenobiotics and their reactive intermediates bind to cellular macromolecules and/or generate oxidative stress. which provoke deleterious effects on the cell function. Induction of xenobiotic-biotrans-forming enzymes and antioxidant molecules is an important defense mechanism against such insults. A group of genes involved in the defense mechanism. e.g. genes encoding glutathione S-transferases. NAD(P)H: quinone oxidoreductase, UDP-glucuronosyltransferase (UDP-GT) and ${\gamma}$-glutamylcysteine synthetase (GGCS). have a common regulatory sequence, Antioxidant or Electrophile Responsive Element (ARE/EpRE). Recently. Nrf2. discovered as a homologue of erythroid transcription factor p45 NF-E2, was shown to bind ARE/EpRE and induce the expression of these defense genes. Mice that lack Nrf2 show low basal levels of expression and/or impaired induction of these genes. which makes the animals highly sensitive to xenobiotic toxicity. Indeed. we show here that nrf2-deficient mice had a higher mortality than did the wild-type mice when exposed to acetaminophen (APAP). Detailed analyses of APAP hepatotoxicity in the nrf2 knockout mice indicate that a large amount of reactive APAP metabolites was generated in the livers due to the impaired basal expression of two detoxifying enzyme genes, UDP-GT (Ugt1a6) and GGCS. while the cytochrome P450 content was unchanged. Thus. the studies using the nrf2 knockout mice clearly demonstrate significance of the expression of Nrf2-regulated enzymes in protection against xenobiotic toxicity.

• Development and Reproduction
• /
• v.24 no.1
• /
• pp.31-41
• /
• 2020

We investigated the effects of endoplasmic reticulum (ER) stress inhibitor and antioxidant treatments during the micromanipulation of somatic cell nuclear transfer (SCNT) on in vitro development of SCNT embryos. Tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor and vitamin C (Vit. C), an antioxidant, were treated by alone or in combination, then, the level of X-box binding protein 1 (Xbp1) splicing and the expressions of ER stress-associated genes, oxidative stress-related genes, and apoptotic genes were confirmed in the 1-cell and blastocyst stages. In the 1-cell stage, the levels of Xbp1 splicing were significantly decreased in TUDCA and Vit. C treatment groups compared to the control (p<0.05). In addition, the expression levels of most ER stress-associated genes and oxidative stress-related genes were significantly lower in all treatment groups than the control (p<0.05), and the transcript levels of apoptotic genes were also significantly lower in all treatment groups than the control (p<0.05). In the blastocyst stage, decreased expression of ER stress-, oxidative stress-, and apoptosis-related genes were observed only in some treatments. However, the blastocyst formation rates in TUDCA and Vit. C treatment groups (24.8% and 22.0%, respectively) and mean blastocyst cell number in all treatment groups (59.7±4.3 to 63.5±3.3) were significantly higher (p<0.05) than those of control. The results showed that the TUDCA or Vit. C treatment during micromanipulation inhibited both ER and oxidative stresses in the early stage of SCNT embryos, thereby reducing cell damage and promoting in vitro development.

• BMB Reports
• /
• v.37 no.2
• /
• pp.139-143
• /
• 2004

The antioxidant responsive element (ARE) is a cis-acting regulatory element of genes encoding phase II detoxification enzymes and antioxidant proteins, such as NAD(P)H: quinone oxidoreductase 1, glutathione S-transferases, and glutamate-cysteine ligase. Interestingly, it has been reported that Nrf2 (NF-E2-related factor 2) regulates a wide array of ARE-driven genes in various cell types. Nrf2 is a basic leucine zipper transcription factor, which was originally identified as a binding protein of locus control region of ss-globin gene. The DNA binding sequence of Nrf2 and ARE sequence are very similar, and many studies demonstrated that Nrf2 binds to the ARE sites leading to up-regulation of downstream genes. The function of Nrf2 and its downstream target genes suggests that the Nrf2-ARE pathway is important in the cellular antioxidant defense system. In support of this, many studies showed a critical role of Nrf2 in cellular protection and anti-carcinogenicity, implying that the Nrf2-ARE pathway may serve as a therapeutic target for neurodegenerative diseases and cancers, in which oxidative stress is closely implicated.

• Proceedings of the KSAR Conference
• /
• 2003.06a
• /
• pp.47-47
• /
• 2003

The present study was conducted to determine the expression of the antioxidant enzyme(CuZn-SOD, Mn-SOD and GPX and apoptosis gene(caspase-3) for in vitro culture in in vitro maturation and in vitro fertilization(IVM/IVF) embryos in porcine. Porcine embryos derived from IVM/IVF were cultured in NCSU23 medium under 5% $CO_2$ in air at 38.5$^{\circ}C$. The patterns of gene expression for several antioxidant enzyme and apoptosis genes during preimplantion porcine embryo development were examined by the modified semi-quantitative single cell reverse transcriptase- polymerase chain reaction (RT-PCR). Preimplantation porcine embryos produced by IVM/IVF have expressed mRNAs for CuZn-SOD and GPX, whereas transcripts for Mn-SOD have not detected at any developmental stages. Expression of caspase-3 mRNA was detected at 2 cell, 8 cell, 16 cell and morula stages. The fas ligand transcripts were detected in porcine blastocyst. These results suggest that various antioxidant enzymes and apoptosis genes play crucial roles in in vitro culture of porcine IVM/IVF embryos.

• The Journal of Korean Medicine
• /
• v.24 no.2
• /
• pp.148-158
• /
• 2003

Backgrounds & Objectives: In many recent studies, molecular biological methods have been used to investigate the role of cytokines in pathogenesis and new therapeutic targets of asthma. Recently, as a method of research on the gene expression, they are applying another method which assays multiple gene expressions at the same time by the microarray. In this study, the antioxidant effect, the inhibitory effect against interleukin-4 and the effect on the CD/cytokine gene expression in PBMC (peripheral blood mononuclear cells) was evaluated by using cDNA microarray chip of Chungsangboha-tang. Methods: Experimental studies were performed for the antioxidant effect of Chungsangboha-tang on DPPH (1, 1-diphenyl-2-picrylhydrazyl) solution, for the IL-4-inhibiting effect on BALB/c mouse spleen, and for the gene expression effect on PBMC (peripheral blood mononuclear cells) with microarray. Results: Chungsangboha-tang showed antioxidant effect dose-dependently. Chungsangboha-tang inhibited interleukin-4 dose-dependently and showed significant difference in 10ug/ml and 100ug/ml of test groups. There was no 2 more times upregulated genes than in the control group by using cDNA microarray chip of Chungsangbohn-tang, but there were 140%-200% upregulated genes. There was no 2 more times downregulated genes than in the control group by using cDNA microarray chip of Chungsangboha-Tang, but there was 50%-75% downregulated genes. Conclusions: This study showed that Chungsangboha-tang has an antioxidant effect and inhibition of Interleukin-4, but further studies are necessary with microarray.

• Journal of Applied Biological Chemistry
• /
• v.48 no.1
• /
• pp.1-6
• /
• 2005

Analysis of chlorophyll (Chl) fluorescence implicated treatment of 40 mM NaCl decreased maximal photochemical efficiency of photosystem II (PSII) (Fv/Fm), actual quantum yield of PSII (${\Phi}_{PSII}$), and photochemical quenching (qP) in rice, but increased non-photochemical quenching (NPQ). Decreases in Fv/Fm, ${\Phi}_{PSII}$, and qP were significantly alleviated by $30\;{\mu}M$ jasmonic acid (JA), while NPQ increase was enhanced. Transcription levels of antioxidant isoenzyme genes were differentially modulated by NaCl treatment. Expression of cCuZn-SOD2 gene increased, while those of cAPXb, CATb, and CATc genes decreased. JA prevented salt-induced decrease of pCuZn-SOD gene expression, but caused greater decrease in mRNA levels of cAPXa and Chl_tAPX genes. Investigation of vacuolar $Na^+/H^+$ exchanger (NHX2) and 1-pyrroline-5-carboxylate synthetase (P5CS) gene expressions revealed transcription level of NHX2 gene was increased by JA, regardless of NaCl presence, while that of P5CS gene slightly increased only in co-presence of JA and NaCl. Unlike JA, ${\gamma}$-radiation rarely affected expressions of antioxidant isoenzyme, NHX2, and P5CS genes, except for increase in mRNA level of Chl_tAPX and decrease in that of pCuZn-SOD. These results demonstrate enhanced salt-tolerance in JA-treated rice seedlings may be partly due to high transcription levels of pCuZn-SOD, NHX2, and P5CS genes under salt stress.

• Asian-Australasian Journal of Animal Sciences
• /
• v.17 no.1
• /
• pp.33-38
• /
• 2004

This study was aimed at testing the gene expression of antioxidant enzymes and apoptosis genes for in vitro culture in porcine embryos produced by in vitro maturation/in vitro fertilization (IVM/IVF). Pocine preimplantation embryos obtainted from IVM/IVF can be successfully culture in vitro, but they are delayed or stop to develop at specific developmental stage. Many factors such as reactive oxygen species and apoptosis in an IVM/IVF system followed by in vitro culture influence the rate of production of viable blastocysts. Porcine embryos derived from IVM/IVF were cultured in the atmosphere of 5% $CO_2$ and 20% $O_2$ at $38.5^{\circ}C$ in NCSU23 medium. The patterns of gene expression for antioxidant enzymes and apoptosis genes during in vitro culture in pocine IVM/IVF embryos were examined by the modified semi-quantitative single cell reverse transcriptase-polymerase chain reaction (RT-PCR). Porcine embryos produced by in vitro procedures were expressed mRNAs for CuZn-SOD, GAPDH and GPX, whereas transcripts for Mn-SOD and catalase were not detected at any developmental stages. Expression of caspase-3 mRNA was detected at 2 cell, 8 cell 16 cell and blastocyst, but p53 mRNA was not detected at any stages. The fas transcripts was only detected in blastocyst stage. These results suggest that various antioxidant enzymes and apoptosis genes play crucial roles in vitro culture of porcine IVM/IVF embryos.

• Journal of Microbiology and Biotechnology
• /
• v.26 no.2
• /
• pp.277-286
• /
• 2016

Makgeolli lees (ML) has several physiological effects such as antioxidant, antidiabetic, and anticancer properties, but its biological functions have not been determined definitively. Here, we tested whether ML has a cytoprotective effect on paraquat (PQ)-induced oxidative stress in the human lung carcinoma cell line A549. At 0.1 mg/ml ML, viability of PQ-exposed A549 cells was restored by 12.4%, 18.5%, and 48.6% after 24, 48, and 72 h, respectively. ML also reduced production of the intracellular reactive oxygen species (ROS) that were generated by PQ treatment. Further experiments revealed that ML treatment enhanced the expression and nuclear translocation of nuclear factor erythroid 2-related factor 2 (NRF2) as well as ARE-GFP reporter activity. ML treatment also effectively increased the expression of NRF2's target genes NAD(P)H dehydrogenase quinone 1 (NQO1) and heme oxygenase 1 (HO-1). Moreover, we found that expression of cytoprotective genes, including glutathione peroxidases (GPXs), superoxide dismutase (SOD1), catalase (CAT), peroxiredoxin 3 (PRDX3), and peroxiredoxin 4 (PRDX4), was greatly enhanced by treatment with ML during PQ exposure. Taken together, the data suggest that treatment of PQ-exposed A549 cells with ML ameliorates cytotoxicity through induction of NRF2 expression and its target genes HO-1, NQO1, and other antioxidant genes. Thus, ML may serve as a functional food applicable to ROS-mediated human diseases.

• The Korea Journal of Herbology
• /
• v.33 no.1
• /
• pp.1-7
• /
• 2018

Objectives : Puerariae Radix extracts are a rich source of isoflavones that affect the activity of hepatic antioxidant enzymes. However, the effect of these extracts on hair growth in human dermal papilla (DP) cells is unknown. The purpose of this study is to compare the effects between juice and water extracts of Puerariae Radix on the mRNA expression levels of hair growth-related genes in dermal papilla (DP) cells. Methods : The antioxidant activity of juice and water extracts of Puerariae Radix was analyzed using an ABTS assay. The cytotoxicity was analyzed using the MTS assay in DP cells. mRNA expression levels of hair growth-related genes in dermal papilla (DP) cells were analyzed using quantitative RT-PCR analysis. Results : Juice and water extracts of Puerariae Radix showed strong antioxidant activity. The cytotoxicity was confirmed to be higher in the juice extract than the water extract, using the MTS assay on DP cells. The mRNA expression levels of CTNNB1, FGF7, and BMP6 were significantly increased after treatment with water extract, whereas the juice extract did not affect the expression of hair growth-related genes. Conclusions : Our study provides evidence that water extract of Puerariae Radix is effective at inducing hair growth, by promoting the mRNA expression levels of hair growth-related genes. Also in the future, studies should be conducted to investigate the effects of Puerariae radix extracts on the various hair growth mechanisms of dermal papilla cells.