• Molecular & Cellular Toxicology
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• 제3권4호
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• pp.231-237
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• 2007

Exposure to DNA-damaging agents can elicit a variety of stress-related responses that may alter the expression of genes associated with numerous biological pathways. We used 19 k whole human genome chip to detect gene expression profiles and potential signature genes in human normal hepatocytes (THLE-3) by treatment of five direct acting mutagens, furylfuramide (AF-2), N-nitroso-N-methylurea (MNU), methylmethanesulfonate (MMS), 4-nitroquinoline-N-oxide (4-NQO) and 2-nitrofluorene (2NF) of the $IC_{20}$ concentration for 3 h. Fifty one up-regulated common genes and 45 down-regulated common genes above 1.5-fold by five direct-acting mutagens were identified by clustering analysis. Many of these changed genes have some association with apoptosis, control of cell cycle, regulation of transcription and signal transduction. Genes related to these functions, as TP73L, E2F5, MST016, SOX5, MAFB, LIF, SII3, TFIIS, EMR1, CYTL1, CX3CR1 and RHOH are up-regulated. Down-regulated genes are ALOX15B, xs155, IFITM1, BATF, VAV2, CD79A, DCDC2, TNFSF8 and KOX8. We suggest that gene expression profiling on mutagens by toxicogenomic analysis affords promising opportunities to reveal potential new mechanistic markers of genotoxicity.

• 대한의생명과학회지
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• 제10권1호
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• pp.15-21
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• 2004

Vitamin $D_3$ up-regulated protein 1 (VDUP1) gene is known to be a novel member of early response genes as an oxidative stress mediator. To elucidate role of VDUP1 expression in neuronal injury, VDUP1 gene expression and histological change were tested in the spinal cords after traumatic spinal cord injury (SCI) in young and adult rats. VDUP1 transcript was detected weakly in a few cells in the spinal cords of control young and adult rats. VDUP1 transcript was increased in the contused spinal cords 1 day after SCI in both young and adult rats. VDUP1 transcript was decreased in the spinal cords 7 days after SCI in young rats. However, VDUP1 transcript was not decrease significantly 7 days in the spinal cords after SCI in adult rats. Cell damage in the spinal cords and hind limb dysfunction were more prominent 7 days after SCI in adult rats compared with that in young rats. These data show that VDUP1 may be involved in neurodegeneration after traumatic SCI.

• 대한한방내과학회지
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• 제32권2호
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• pp.243-258
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• 2011

Objectives : This study investigated the hypolipidemic and antioxidant effects of Curcuma radix using a rat model induced by poloxamer 407 injection. Methods : Serum lipid parameters and oxidative stress-associated biomarkers were determined. Additionally, hepatic cholesterol and triglyceride as well as lipid metabolism-associated gene expressions were observed in hepatic tissue. Results : 1. Curcuma radix ameliorated elevation of serum cholesterol, triglyceride, LDL-cholesterol, MDA, hepatic cholesterol level, and reduction of serum TAC, SOD, GSH, GSH-reductase level. 2. Curcuma radix augmented up-regulated ACAT gene expression. 3. Curcuma radix almost completely ameliorated down-regulated CYP-7A1 but up-regulated HMG-CoA gene expression. Conclusions : The hypolipidemic and antioxidant properties of Curcuma radix were evidenced. This study provides a scientific basis for the clinical application of Curcuma radix and development of hypolipidemics using this herb in the future.

• International Journal of Industrial Entomology and Biomaterials
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• 제6권2호
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• pp.157-162
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• 2003

The glutathione S-transferase (GSTs) are enzymes responsible for the protection of cells from chemical toxicants and oxidative stress. We describe here the cDNA sequence and mRNA expression of a putative GST from the mole cricket, Gryllotalpa orientalis. The G. orientalis GST cDNA sequences comprised of 621 bp encoding 207 amino acid residues. The multiple sequence alignment of G. orientalis GST gene with other known insect GSTs showed several conserved residues that may be essential for the enzymatic activity of the protein. Phylogenetic analysis of the deduced amino acid sequences of G. orientalis GST gene with other insect GST sequences revealed that the G. orientalis GST gene belongs to class I GST, forming a strong monophyletic group (100% bootstrap value) exclusively for class I GSTs from a diverse insect species. Northern blot analysis confirmed midgut-specific expression at transcriptional level, evidencing the midgut as a site for GST synthesis.

• 한국인삼전략화협의회:학술대회논문집
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• 한국인삼전략화협의회 2003년도 제4차 한국인삼약초산업 전략화 세미나
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• pp.54-63
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• 2003

"Korea ginseng (Panax ginseng C.A Meyer) is an important medicinal plant. Its root has been used as an herbal medicine that provides resistance to stress and disease, and prevents exhaustion since the ancient time. Ginsenosides, glycosylated triterpene (saponin), are considered to be the main active compounds of the ginseng root. Despite of considerable commercial interests of ginsenosides, very little is known about the genes and their biochemical pathways for ginsenoside biosynthesis. This work will focus on the identification of genes involved in ginsenoside biosynthesis and the dissection of ginsenoside biosynthetic pathway using a functional genomics tool. Expression sequence tags (ESTs) provide a valuable tool to discovery the genes in secondary metabolite biosynthesis. We generated over 21,155 ginseng ESTs that is now sufficient to facilitate discovering the genes involved in ginsenoside biosynthesis such as oxidosqualene cyclase(OSC), cytochrome P450 and glycosyltransferase. With ESTs information, microarray technology will be used for the analysis of gene expression, and the identification of genes including transcription factors expressed in tissues under given experimental condition. Heterogous system such as yeast and plants will allow us to do the functional analysis. And selected ginseng hairy root which show variation in ginsenoside production will be used as a material for functional analysis of candidate gene. Functional genomics approach will successfully accelerate gene discovery, and also provide promises of metabolic engineering for the ginsenoside production."

• Asian Pacific Journal of Cancer Prevention
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• 제16권12호
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• pp.4803-4812
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• 2015

Chronic alcohol and tobacco abuse plays a crucial role in the development of different liver associated disorders. Intake promotes the generation of reactive oxygen species within hepatic cells exposing their DNA to continuous oxidative stress which finally leads to DNA damage. However in response to such damage an entangled protective repair machinery comprising different repair proteins like ATM, ATR, H2AX, MRN complex becomes activated. Under abnormal conditions the excessive reactive oxygen species generation results in genetic predisposition of various genes (as ADH, ALDH, CYP2E1, GSTT1, GSTP1 and GSTM1) involved in xenobiotic metabolic pathways, associated with susceptibility to different liver related diseases such as fibrosis, cirrhosis and hepatocellular carcinoma. There is increasing evidence that the inflammatory process is inherently associated with many different cancer types, including hepatocellular carcinomas. The generated reactive oxygen species can also activate or repress epigenetic elements such as chromatin remodeling, non-coding RNAs (micro-RNAs), DNA (de) methylation and histone modification that affect gene expression, hence leading to various disorders. The present review provides comprehensive knowledge of different molecular mechanisms involved in gene polymorphism and their possible association with alcohol and tobacco consumption. The article also showcases the necessity of identifying novel diagnostic biomarkers for early cancer risk assessment among alcohol and tobacco users.

• Journal of Plant Biotechnology
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• 제37권1호
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• pp.72-76
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• 2010

To develop transgenic cucumber tolerant to abiotic stress, a cotyledonary-node explants were co-cultivated with Agrobacterium tumefaciens (EHA101) carrying TPSP gene (pHC30-TPSP). After transfer to fresh medium every two week for eight weeks, putative transgenic plants were selected when shoots grown a length greater than 3 cm from the cotyledonary-node explants on selection medium supplemented with $5\;mgl^{-1}$ phospinotricin as selectable agent. The confirmation of transgenic cucumber was based on the Northern blot analysis. Thirty four shoots (5.2%) with resistance to phospinotricin were obtained from 660 explants inoculated. Of them, transformants were only confirmed from 11 plants (1.7%). Transgenic cucumber expressing TPSP gene was more synthesized at 3.8 times amounts of trehalose (0.014 mg g fresh $wt^{-1}$) than non-transformants (0.0037 mg g fresh $wt^{-1}$). However, all of transgenic plants showed abnormal morphology, including stunted growth (< height 15 cm), shrunken leaves, and sterility as compared with non-transgenic plants (> height 150 cm) under the same growth environment. These results lead us to speculate that the overproduction of trehalose was toxic for cucumber, even though that had known for rice as non-toxic.

• Molecular & Cellular Toxicology
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• 제4권4호
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• pp.293-299
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• 2008

To screen the differentially expressed genes in cadmuim-exposed marine medaka fish (Oryzias javanicus), a candidate marine test fish for ecological toxicity, the differential display polymerase chain reaction (DD-PCR) was carried out, since the genome-wide gene expression data are not available in this fish species yet. A total of 35 clones were isolated from cadmium-exposed fish and their nucleotide sequences were analyzed. The differentially expressed gene candidates were categorized to response to stimulus (3); ion binding (3); DNA binding (1); protein binding (6); carbohydrate binding (1); metabolic process (4); biological regulation (3); cellular process (2); protein synthesis (2); catalytic activity (2); sense of sight (1); immune (1); neurohormone (1); signaling activity (1); electron carrier activity (1) and others (3). For real-time quantitative RT-PCR, we selected catalase, glucose-6-phosphate dehydrogenase, heat shock protein 70, and metallothionein and confirmed that cadmium exposure enhanced induction of these four genes.

• Animal cells and systems
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• 제7권3호
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• pp.173-186
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• 2003

The transition metal cadmium is a serious occupational and environmental toxin. To inhibit cadmium-induced damage, cells respond by increasing the expression of genes that encode stress-responsive proteins. The metal-regulatory transcription factor 1 (MTF-1) is a key regulator of heavy-metal induced transcription of metallothionein-I and II and other genes in mammals and other metazoans. Transcriptional activation of genes by MTF-1 is mediated through binding to metal-responsive elements in the target gene promoters. Phosphorylation of MTF-1 plays a critical role in the cadmium-inducible transcriptional activation of metallothionein and other responses. Studies using inhibitors indicate that multiple kinases and signal transduction cascades, including those mediated by protein kinase C, tyrosine kinase and casein kinase II, are essential for cadmium-mediated transcriptional activation. In addition, calcium signaling is also involved in regulating metal-activated transcription. In several species, cadmium induces heat shock genes. Recently much progress has been made in elucidating the cellular machinery that regulates this metal-inducible gene expression. This review summarizes these recent advances in understanding the role of some known cadmium-responsive genes and the molecular mechanisms that activate metal-responsive transcription factor, MTF-1.

• Journal of Microbiology and Biotechnology
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• 제21권3호
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• pp.243-251
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• 2011

The gene bolA was discovered in the 80's, but unraveling its function in the cell has proven to be a complex task. The BolA protein has pleiotropic effects over cell physiology, altering growth and morphology, inducing biofilm formation, and regulating the balance of several membrane proteins. Recently, BolA was shown to be a transcription factor by repressing the expression of the mreB gene. The present report shows that BolA is a transcriptional regulator of the dacA and dacC genes, thus regulating both DD-carboxypeptidases PBP5 and PBP6 and thereby demonstrating the versatility of BolA as a cellular regulator. In this work, we also demonstrate that reduction of cell growth and survival can be connected to the overexpression of the bolA gene in different E. coli backgrounds, particularly in the exponential growth phase. The most interesting finding is that overproduction of BolA affects bacterial growth differently depending on whether the cells were inoculated directly from a plate culture or from an overnight batch culture. This strengthens the idea that BolA can be engaged in the coordination of genes that adapt the cell physiology in order to enhance cell adaptation and survival under stress conditions.