• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제34권6호
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• pp.602-610
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• 2008

Purpose Acrylamide is present in significant quantities in a wide range of commonly consumed human foods. Carcinogenic risk of acrylamide through the consumption of food is a great public concern and in controversy, but it is not properly addressed due to the lack of evidence in humans. While a plenty of data is available on the carcinogenicity in animal models, the studies in humans are limited. Thus, the present study attempted to examine the carcinogenic potentials of acrylamide on the human epithelial cell, which is the target cell origin of the most cancers. Material and method & Result 1. Acrylamide was not cytotoxic up to $100{\mu}M$ as measured by MTT and LDH assays, indicating a relatively low toxicity of this substance in human epithelial cells. 2. The parameters of neoplastic cellular transformation such as cell saturation density, soft-agar colony formation and cell aggregation were analyzed to examine the carcinogenic potential of acrylamide. 3. The neoplastic transformation was further increased with the co-treatment of TPA 4. Antioxidants blocked the generation of Reactive Oxygen Species(ROS) and the GSH depleting agent dramatically increased the ROS production. 5. mRNA levels of fibronectin following acrylamide exposure was increased in a dose-dependent manner, indicating a possible biomarker of acrylamide-induced cellular transformation. Conclusion The present study will provide a valuable basis to compare the interspecies differences in response to carcinogenic potentials of acrylamide. The data on the interspecies differences are essential element in human risk assessment. Thus, our results obtained from the human epithelial cells will contribute to improving the risk assessment of human neoplasm including oral cancer.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2005년도 춘계학술대회
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• pp.53-60
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• 2005

Parkinson's disease (PD) is a progressive neurodegenerative disorder affecting $1\%$ of the population above the age of 65 and is characterized by a selective loss of dopaminergic neurons in the substantia nigra pars compacta. Although the underlying cause of dopaminergic cell death or the mechanism by which these cells degenerate is still not clearly understood, oxidative stress, mitochondrial dysfunction, and protein misfolding are thought to play important roles in the dopaminergic degeneration in PD. Tetrahydrobiopterin (BH4) is synthesized exclusively in the monoaminergic, including dopaminergic, cells and serves as an endogenous and obligatory cofactor for syntheses of the potential oxidative stressors dopamine and nitric oxide. In addition to its contribution toward the syntheses of these two potentially toxic molecules, BH4 itself can directly generate oxidative stress. BH4 undergoes oxidation during the hydroxylation reaction as well as nonenzymatic autooxidation to produce hydrogen peroxide and superoxide radical. We have previously suggested BH4 as an endogenous molecule responsible for the dopaminergic neurodegeneration. BH4 exerts selective toxicity to dopamine-producing cells via generation of oxidative stress, mitochondrial dysfunction, and apoptosis. BH4 also induces morphological, biochemical, and behavioral characteristics associated with PD in vivo. BH4 as well as enzyme activity and gene expression of GTP cyclohydrolase I, the rate-limiting enzyme in BH4 synthesis pathway, are readily upregulated by cellular changes such as calcium influx and by various stimuli including stress situations. This points to the possibility that cellular availability of BH4 might be increased in aberrant conditions, leading to increased extracellular BH4 subsequent degeneration. The fact that BH4 is specifically and endogenously synthesized in dopaminergic cells, Is readily upregulated, and generates oxidative stress-related cell death provides physical relevance of this molecule as an attractive candidate with which to explain the mechanism of pathogenesis of PD.

• Molecular & Cellular Toxicology
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• 제1권1호
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• pp.62-71
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• 2005

For toxicity model in the kidney, renal cell carcinoma (RCC) is one of the most important model to assess the structural and functional alterations. Most RCCs are sporadic, and environmental agents are suspected to play a role in the etiology of the disease. In this study, we discovered novel evidence for previously unknown gene expression patterns related to progression according to cancer stage in RCC. Four clear cell RCC tissue samples along with five corresponding patient-matched normal kidney tissue samples were obtained from patients undergoing partial or radical nephrectomy. To examine the difference of gene expression profile in clear cell RCC, radioactive cDNA microarrays were used to evaluate changes in the expression of 1,152 genes in a total. Using $^{33}P-labeled$ probes, this method provided highly sensitive gene expression profiles including drug metabolism, and cellular signaling. 29 genes were identified with expression levels that differed by more than 2.0 value of z-ratio, compared with that in control. Whereas expression of 38 genes were decreased by less than-2.0 value of z-ratio. In conclusion, this study has identified 67 gene expression alterations in clear-cell type of RCC. Most notably, genes involved in cell growth were up-regulated in stage I more than stage III whereas genes involved in signal transduction were down-regulated in which both stage I and stage III. The identified alteraions of gene expression will likely give in sight in to clear cell RCC and tumor progression.

• 동의신경정신과학회지
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• 제24권3호
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• pp.309-320
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• 2013

Objectives : There is a possibility LRE as remedy in Alzheimer disease (AD), but it's nerve protection effect and mechanism have to be elucidate. In this research, we applied LRE on $A{\beta}_{25-35}$ pre-treated SH-SY5Y cells, to find out the nerve protection effect and mechanism in AD cell model. Methods : We tried to confirm that effect by experimenting with 20, 50, and $100{\mu}g/ml$ concentration of LRE as a medicine. Next experiment, we assessed damage effect which induced $A{\beta}_{25-35}$, known to cause AD, on SH-SY5Y cell. In addition, cellular viability test is executed under $H_2O_2$ treatment condition in a SH-SY5Y cell. Results : 1. In $A{\beta}_{25-35}$ treated SH-SY5Y cell, LRE exhibited an anti-phosphorylation effect about tau protein, JNK, and IKB. 2. LRE prevent nerve cell apoptosis, which indued $A{\beta}_{25-35}$ and oxidative stress, modify JNK engaged synaptic structure and $NF{\kappa}B$ induced p75-neurotrophin receptor polymorphism. Conclusions : We found that LRE prevented oxidative stress-induced cellular destruction, for example, increased SOD activity of $A{\beta}_{25-35}$ treated SH-SY5Y cell and reduced toxicity of oxygen free radical. Consequently, the ingredients of LRE have a role as a catalyzer for $A{\beta}_{25-35}$ clearance and as scavenger for active oxygen free radical.

• Journal of Microbiology and Biotechnology
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• 제18권8호
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• pp.1431-1438
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• 2008

Immunomodulating activities of water-soluble exopolysaccharides (LL-EX) obtained from submerged mycelial culture of Lentinus lepideus were studied and their effectiveness was compared with lipopolysaccharide (LPS). The influence of the LL-EX on macrophage cellular lysosomal enzyme activity was to stimulate up to 267%, 392%, and 464% at the level of 10, 50, and $100{\mu}g/ml$, respectively. When the LL-EX was further fractionated into LL-Fr.I and Fr.II by Sepharose CL-6B gel chromatography, the cellular lysosomal enzyme activity of LL-Fr.II (2.1-fold) was higher than Fr.I (1.2-fold). Moreover, both LL-Fr.I and Fr.II stimulated the cytokines IL-1$\beta$, TNF-$\alpha$, and IL-6 in macrophages. In mixed lymphocyte reaction, LL-Fr.I and Fr.II enhanced the splenocyte proliferation up to 1.2-fold and 1.4-fold ($50{\mu}g/ml$), respectively, stimulating only T lymphocytes. The fractions of LL-EX not show any direct toxicity against human gastric adenocarcinoma cell (AGS). The molecular masses of LL-Fr.I and Fr.II were estimated to be about 1,986 kDa and 21 kDa, respectively. The total sugar and protein contents of the two fractions were 84.97% and 69.88%, and 15.03% and 30.12%, respectively. The sugar and amino acid compositions of the LL-Fr.I and Fr.II were also analyzed in detail.

• The Korean Journal of Physiology and Pharmacology
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• 제8권3호
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• pp.117-127
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• 2004

The heterodimeric amino acid transporter family is a subfamily of SLC7 solute transporter family which includes 14-transmembrane cationic amino acid transporters and 12-transmembrane heterodimeric amino acid transporters. The members of heterodimeric amino acid transporter family are linked via a disulfide bond to single membrane spanning glycoproteins such as 4F2hc (4F2 heavy chain) and rBAT $(related\;to\;b^0,\;^+-amino\;acid\;transporter)$. Six members are associated with 4F2hc and one is linked to rBAT. Two additional members were identified as ones associated with unknown heavy chains. The members of heterodimeric amino acid transporter family exhibit diverse substrate selectivity and are expressed in variety of tissues. They play variety of physiological roles including epithelial transport of amino acids as well as the roles to provide cells in general with amino acids for cellular nutrition. The dysfunction or hyperfunction of the members of the heterodimeric amino acid transporter family are involved in some diseases and pathologic conditions. The genetic defects of the renal and intestinal transporters $b^{0,+}AT/BAT1\;(b^{0,+}-type\;amino\;acid\;transporter/b^{0,+}-type\;amino\;acid\;transporter\;1)$ and $y^+LAT1\;(y^+L-type\;amino\;acid\;transporter\;1)$ result in the amino aciduria with sever clinical symptoms such as cystinuria and lysin uric protein intolerance, respectively. LAT1 is proposed to be involved in the progression of malignant tumor. xCT (x-C-type transporter) functions to protect cells against oxidative stress, while its over-function may be damaging neurons leading to the exacerbation of brain damage after brain ischemia. Because of broad substrate selectivity, system L transporters such as LAT1 transport amino acid-related compounds including L-Dopa and function as a drug transporter. System L also interacts with some environmental toxins with amino acid-related structure such as cysteine-conjugated methylmercury. Therefore, these transporter would be candidates for drug targets based on new therapeutic strategies.

• Bulletin of the Korean Chemical Society
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• 제32권9호
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• pp.3327-3332
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• 2011

Antimicrobial peptides have recently gained the much attention because of their ability to make defense system from attacking bacterial infections. Drosocin has been considered as very attractive antibiotic agents because of low toxicity against human erythrocytes and active at the low concentration. We have studied the structureactivity relationship of a glycopeptide drosocin focused on the N-acetyl-D-galactoside at $Thr^{11}$ residue. Based on the radial diffusion assay, we found that the acetylation of carbohydrate moiety increased the antimicrobial activity and the $Pro^{10}$, present in the middle of drosocin plays an important role in the antimicrobial activity. Our results provide a good lead compound for further studies on the design of drosocin-based analogues targeting glyco linked Thr site.

• Molecular & Cellular Toxicology
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• 제5권1호
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• pp.67-74
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• 2009

Exposures to environmental chemicals that mimic endogenous hormones are proposed for a number of adverse health effects, including infertility, abnormal prenatal and childhood development and above all cancers. In addition, recently miRNA (micro RNA) has been recognized to play an important role in various diseases and in cellular and molecular responses to toxicants. In this study, endocrine disrupting environmental toxicant, nonylphenol (NP) was treated to MCF-7 (Human breast cancer cell) and HepG2 (Human hepatocellular liver carcinoma) cell line at 3 hrs and 48 hrs time point and miRNA analysis using $mirVana^{TM}$ miRNA bioarray was performed and compared with total mRNA microarray data for the same cell line and treatment. Robust data quality was achieved through the use of dye-swap. Analysis of microarray data identifies a total of 20 and 11 miRNA expressions at 3 hrs and 48 hrs exposure to NP in MCF-7 cell line and a total of 14 and 47 miRNA expression at 3 hrs and 48 hrs exposure respectively to NP in HepG2 cell line. Expression profiling of the selected miRNA (let-7c, miR-16, miR-195, miR-200b, miR200c, miR-205, and miR-589) reveals changes in the expression of target genes related to metabolism, immune response, apoptosis, and cell differentiation. The present study can be informative and helpful to understand the role of miRNA in molecular mechanism of chemical toxicity and their influence on hormone dependent disease. Also this study may prove to be a valuable tool for screening potential estrogen mimicking pollutants in the environment.

• Molecules and Cells
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• 제37권9호
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• pp.672-684
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• 2014

The exact causes of cell death in Parkinson's disease (PD) remain unknown despite extensive studies on PD.The identification of signaling and metabolic pathways involved in PD might provide insight into the molecular mechanisms underlying PD. The neurotoxin 1-methyl-4-phenylpyridinium ($MPP^+$) induces cellular changes characteristic of PD, and $MPP^+$-based models have been extensively used for PD studies. In this study, pathways that were significantly perturbed in $MPP^+$-treated human neuroblastoma SH-EP cells were identified from genome-wide gene expression data for five time points (1.5, 3, 9, 12, and 24 h) after treatment. The mitogen-activated protein kinase (MAPK) signaling pathway and endoplasmic reticulum (ER) protein processing pathway showed significant perturbation at all time points. Perturbation of each of these pathways resulted in the common outcome of upregulation of DNA-damage-inducible transcript 3 (DDIT3). Genes involved in ER protein processing pathway included ubiquitin ligase complex genes and ER-associated degradation (ERAD)-related genes. Additionally, overexpression of DDIT3 might induce oxidative stress via glutathione depletion as a result of overexpression of CHAC1. This study suggests that upregulation of DDIT3 caused by perturbation of the MAPK signaling pathway and ER protein processing pathway might play a key role in $MPP^+$-induced neuronal cell death. Moreover, the toxicity signal of $MPP^+$ resulting from mitochondrial dysfunction through inhibition of complex I of the electron transport chain might feed back to the mitochondria via ER stress. This positive feedback could contribute to amplification of the death signal induced by $MPP^+$.

• Biomolecules & Therapeutics
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• 제23권5호
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• pp.407-413
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• 2015

Paraquat dichloride (N,N-dimethyl-4-4'-bipiridinium, PQ) is an extremely toxic chemical that is widely used in herbicides. PQ generates reactive oxygen species (ROS) and causes multiple organ failure. In particular, PQ has been reported to be an immunotoxic agrochemical compound. PQ was shown to decrease the number of macrophages in rats and suppress monocyte phagocytic activity in mice. However, the effect of PQ on macrophage cell viability remains unclear. In this study, we evaluated the cytotoxic effect of PQ on the mouse macrophage cell line, RAW264.7 and its possible mechanism of action. RAW264.7 cells were treated with PQ (0, 75, and $150{\mu}M$), and cellular apoptosis, mitochondrial membrane potential (MMP), and intracellular ROS levels were determined. Morphological changes to the cell nucleus and cellular apoptosis were also evaluated by DAPI and Annexin V staining, respectively. In this study, PQ induced apoptotic cell death by dose-dependently decreasing MMP. Additionally, PQ increased the cleaved form of caspase-3, an apoptotic marker. In conclusion, PQ induces apoptosis in RAW264.7 cells through a ROS-mediated mitochondrial pathway. Thus, our study improves our knowledge of PQ-induced toxicity, and may give us a greater understanding of how PQ affects the immune system.