• 한국컴퓨터정보학회논문지
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• 제21권12호
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• pp.139-145
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• 2016

In this paper, we propose to evaluate the effect of Resistin-like molecule alpha (Retnla) on the expression of transporters involved in modulating concentrations of peripheral cholesterol and plasma high-density lipoprotein (HDL) cholesterol. High levels of blood cholesterol are a well-recognized risk factor for atherosclerosis and are eliminated via the process of reverse cholesterol transport (RCT). We recently showed that Retnla ameliorates hypercholesterolemia and atherosclerosis by increasing biliary cholesterol secretion, the final step of the process, in low-density lipoprotein receptor-deficient mice. However, the role of Retnla in HDL-mediated cholesterol efflux, initial step of RCT pathway, is not yet clear. To identify cholesterol transport genes regulated by Retnla, we performed an extensive microarray-based gene expression screen using livers from Retnla-overexpressing (Tg) mice and control animals. The most significant change in Retnla-Tg mice was an upregulation of ATP-binding cassette sub-family G member 4 (Abcg4) transport and was validated using quantitative RT-PCR. The validated gene was also induced by treatment of purified Retnla protein in RAW 264.7 cells incubated with acetylated low-density lipoprotein and Hepa1c1c7 cells. Taken together, these results indicates that Retnla might also accelerate initial step of RCT pathway, suggesting therapeutic value of Retnla in the treatment of hypercholesterolemia and atherosclerosis.

• 동의신경정신과학회지
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• 제18권1호
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• pp.95-110
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• 2007

Objective : The purpose of this study was to investigate molecular basis of neuroprotective effect in total ginsenosides. After H202 induced neurotoxicity, gene expression profiling of SH-SY5Y neuroblastoma cells treated by total ginsenosides is analyzed. Method : After SH-SY5Y cells were cultured, they were damaged by H202 induced oxidative stress. After twenty four hours, experimental group is treated by total ginsenosides and control group is treated by 0.9% saline. A high density cDNA microarray chip is used to analyze the gene expression profiling of SH-SY5Y cells. The Significance Analysis of Microarray method is used for identifying genes on a microarray. Results : 1. According to the results of microarray experiment, 17 genes were up-regulated, 38 genes were down-regulated. 2. Expression of OPHNl, KTANl, ATM, PRKCE, MAPKs genes associated with cell proliferation, neural growth, and the prevention of apoptosis were increased. 3. Change of EPX gene was the greatest among all genes. EPX gene associated with oxidative stress, and tumor suppressor gene ADAM11 were decreased. Conclusion : According to this study, molecular basis of neuroprotective effect of total ginsenosides is as followings: the increase of gene expression associated with cell proliferation, neuron growth, the prevention of apoptotsis and decrease of gene expression associated with oxidative stress and tumor suppressor.

• 대한전기학회논문지:전기물성ㆍ응용부문C
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• 제51권7호
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• pp.328-334
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• 2002

The DNA chips are devices associating the specific recognition properties of two DNA single strands through hybridization process with the performances of the microtechnology. In the literature, the "Gene chip" or "DNA chip" terminology is employed in a wide way and includes macroarrays and microarrays. Standard definitions are not yet clearly exposed. Generally, the difference between macro and microarray concerns the number of active areas and their size, Macroarrays correspond to devices containing some tens spots of 500$\mu$m or larger in diameter. microarrays concern devices containing thousnads spots of size less than 500$\mu$m. The key technical parameters for evaluating microarray-manufacturing technologies include microarray density and design, biochemical composition and versatility, repreducibility, throughput, quality, cost and ease of prototyping. Here we report, a new method in which minute particles are arranged in a random fashion on a chip pattern using random fluidic self-assembly (RFSA) method by hydrophobic interaction. We intend to improve the stability of the particles at the time of arrangement by establishing a wall on the chip pattern, besides distinction of an individual particle is enabled by giving a tag structure. This study demonstrates the fabrication of a chip pattern, immobilization of DNA to the particles and arrangement of the minute particle groups on the chip pattern by hydrophobic interaction.ophobic interaction.

• Journal of Microbiology and Biotechnology
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• 제10권1호
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• pp.21-26
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• 2000

A microarrayer system was developed mainly for manufacturing DNA chips. The 3-axis robot was designed to automatically collect samples from 96-or 384-well microtiter plates using up to 16 simultaneously moving pens and to deposit them on a surface-modified slide glass. This is followed by a wash/dry operation in a clean station. The cycle is repeated with a new set of samples, This system can deposit cDNA or oligonucleotides with spot intervals of $150{\;}\mu\textrm{m}$ and the spot size of $80\mu\textrm{m}$, thus allowing a high density DNA chip containing about 5,000 spots per $\textrm{cm}^2$. The entire procedure is controlled by the Visual C++ program that was written in our laboratory by using a personal computer with Pentium 100 CPU.

• Journal of Microbiology and Biotechnology
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• 제14권4호
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• pp.836-843
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• 2004

Nontypeable H. influenzae (NTHi), a Gram-negative obligate human pathogen, causes pneumonia, chronic bronchitis, and otitis media, and the respiratory epithelium is the first line of defense that copes with the pathogen. In an effort to identify transcriptional responses of human respiratory epithelial cells to infection with NTHi, we examined its differential gene expression using high density cDNA microarrays. BEAS-2B human bronchial epithelial cells were exposed to NTHi for 3 hand 24 h, and the alteration of mRNA expression was analyzed using microarrays consisting of 8,170 human cDNA clones. The results indicated that approximately 2.6% of the genes present on the microarrays increased in expression over 2-fold and 3.8% of the genes decreased during the 24-h infection period. Upregulated genes included cytokines (granulocyte-macrophage colony stimulating factor 2, granulocyte chemotactic protein 2, IL-6, IL-10, IL-8), transcription factors (Kruppel-like factor 7, CCAAT/enhancer binding protein $\beta$, E2F-1, NF-$\kappa$B, cell surface molecules (CD74, ICAM-1, ICAM-2, HLA class I), as well as those involved in signal transduction and cellular transport. Selected genes were further confirmed by reverse-transcription-PCR. These data expand our knowledge of host cellular responses during NTHi infection and should provide a molecular basis for the study of host-NTHi interaction.

• 한국생물정보학회:학술대회논문집
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• 한국생물정보시스템생물학회 2000년도 International Symposium on Bioinformatics
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• pp.74-82
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• 2000

Prostate cancer initially responds and regresses in response to androgen depletion therapy, but most human prostate cancers will eventually recur, and re-grow as an androgen independent tumor. Once these tumors become hormone refractory, they usually are incurable leading to death for the patient. Little is known about the molecular details of how prostate cancer cells regress following androgen ablation and which genes are involved in the androgen independent growth following the development of resistance to therapy. Such knowledge would reveal putative drug targets useful in the rational therapeutic design to prevent therapy resistance and control androgen independent growth. The application of genome scale technologies have permitted new insights into the molecular mechanisms associated with these processes. Specifically, we have applied functional genomics using high density cDNA microarray analysis for parallel gene expression analysis of prostate cancer in an experimental xenograft system during androgen withdrawal therapy, and following therapy resistance, The large amount of expression data generated posed a formidable bioinformatics challenge. A novel template based gene clustering algorithm was developed and applied to the data to discover the genes that respond to androgen ablation. The data show restoration of expression of androgen dependent genes in the recurrent tumors and other signaling genes. Together, the discovered genes appear to be involved in prostate cancer cell growth and therapy resistance in this system. We have also developed and applied tissue microarray (TMA) technology for high throughput molecular analysis of hundreds to thousands of clinical specimens simultaneously. TMA analysis was used for rapid clinical translation of candidate genes discovered by cDNA microarray analysis to determine their clinical utility as diagnostic, prognostic, and therapeutic targets. Finally, we have developed a bioinformatic approach to combine pharmacogenomic data on the efficacy and specificity of various drugs to target the discovered prostate cancer growth associated candidate genes in an attempt to improve current therapeutics.

• Bulletin of the Korean Chemical Society
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• 제25권11호
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• pp.1667-1670
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• 2004

In DNA microarray produced by DNA-deposition technology, DNA-immobilization and -hybridization yields on a solid support are most important factors for its accuracy and sensitivity. We have developed a dendrimeric support using silylated aldehyde slides and polyamidoamine (PAMAM) dendrimers. An oligonucleotide array was prepared through a crosslinking between the dendrimeric support and an oligonucleotide. Both DNAimmobilization and -hybridization yields on the solid support increased by the modification with the dendrimers. The increase of the immobilization and hybridization efficiency seems to result from a threedimensional arrangement of the attached oligonucleotide. Therefore, our dendrimeric support may provide a simple and efficient solution to the preparation of DNA microarrays with high-density DNA-deposition and high hybridization efficiency.

• Genomics & Informatics
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• 제4권1호
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• pp.23-32
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• 2006

In order to investigate the molecular basis of the aging process in brain, we have employed high-density oligonucleotide microarrays providing data on 10,108 gene clusters to define transcriptional patterns in three brain regions, cerebral cortex, cerebellum, and hippocampus. Comparison of the expression patterns between young (6-week-old) and aged (17-month-old) C57BL/6 male micerevealed that about ten percent (1098) of the genes showed a significant change in the expression level in at least one of the three tissues. Among them, 23 genes were upregulated and 62 genes were downregulated in all three tissues of the old mice. The number of genes upregulated exclusively in hippocampus (337) was much larger compared to other tissues. Gene ontology-based analysis showed the genes related with signal transduction or molecular transports are more likely to be upregulated than downregulated in the aging process of hippocampus. These data may provide some useful means for elucidating the molecular aspect of aging in hippocampus and other regions in brain.

• 환경생물
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• 제21권1호
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• pp.52-55
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• 2003

There is considerable evidence that ionizing radiation (IR) mediates checkpoint control, repair and cell death. In this study, we have used a high density microarray hybridization approach to characterize the transcriptional response of human breast carcinoma MCF-7 cell line to ${\gamma}$-radiation, such as 4 Gy 4 hr, 8 Gy 4 hr, and 8 Gy 12 hr. We found that exposure to ${\gamma}$-ray alters by at least a $log_2$ factor of 1.0 the expression of 115 known genes. Of the 66 genes affected by ${\gamma}$-radiation, 49 are down-regulated. In our results, the cellular response to irradiation includes induction of the c-jun and EGR1 early response genes. The present work has examined potential cytoplasmic signaling cascades that transduce IR-induced signals to the nucleus. 40S ribosomal protein s6 kinase modulates the activities of the mitogen activated protein kinase (MAPK) and c-Jun $NH_2$-terminal kinase (JNK1) cascades in human monocytic leukemia (U937/pREP4) cells. 14-3-3 family members are dimeric phosphoserine -binding proteins that participate in signal transduction and checkpoint control pathways.

• Molecular & Cellular Toxicology
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• 제2권2호
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• pp.114-119
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• 2006

Benzo[a]pyrene is a representative ecotoxicant in marine environment and a model compound of polycyclic aromatic hydrocarbons, which has an ability to bioaccumulate in aquatic organisms. This study aimed to identify molecular biomarkers suitable for assessing environmental pollution using a microarray technique. We examined the effects of benzo[a]pyrene on gene expressions in the rockfish, Sebastes schlegeli. We constructed the subtractive cDNA library with hepatic RNA from benzo[a]pyrene-exposed and non-exposed control fish. From the library 10,000 candidate clones were selected randomly and cDNA microarray was constructed. We determined benzo[a]pyrene-responsive genes using a high-density microarray. Statistical analysis showed that approximately 400 genes are significantly induced or reduced by benzo[a]pyrene treatment ($2\;{\mu}m$). Especially gene expression changes of 4 candidate clones among the up- or down-regulated genes were investigated in 6, 12 and 24 hr BaP-exposed fish groups. Many methods have been developed to monitor marine environmental status, which depend on quantifying the levels of the toxic components in polluted seawater or on ecological accessing, such as species diversity or richness. However, those methods could not provide information on physiological or genetic changes induced by such environmental stresses. Comparing with the conventional methods, these data will propose that benzo[a]pyrene-responsive genes can be useful for biological risk assessment of polycyclic aromatic hydrocarbons on marine organism at molecular level.