• YAKHAK HOEJI
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• v.51 no.4
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• pp.264-269
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• 2007

Alzheimer’s disease (AD) is characterized pathologically by the presence of intracellular neurofibrillary tangles and deposition of ${\beta}-amyloid $ (A ${\beta}$) peptides, which are generated by processing of amyloid precursor protein (APP). It is urgent to develop effective therapies for the treatment of AD, since our society rapidly accelerate aging. A${\beta}$ peptides have been believed to be neurotoxic and now are also considered to have effects on the mechanism of memory formation. In this study, effects of radicicol on the metabolism of APP were analyzed. Radicicol inhibited the secretion of A${\beta}$ from the Neuro2a cell line (APPswe cell) expressing APPswe. Beta-site APP cleaving enzyme (BACE) fluorescence resonance energy transfer (FRET) assay revealed that it inhibited BACE activity in a dose dependently manner. Immunoblotting study showed that it inhibited intracellular heat shock protein (HSP)90 and it increased the secretion of HSP90 from the APPswe cells. We suggest that radicicol inhibits APP metabolism and Ap generation by the means of HSP90 inhibitory mechanism and partially BACE inhibitory mechanism. This is the first report that radicicol inhibits the secretion of A${\beta}$ peptides from neuroblastoma cells.

• Korean Journal of Poultry Science
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• v.40 no.1
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• pp.31-40
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• 2013

This study was performed to investigate the investigated effects of dietary supplementation of vitamin C and E on the growth performance and stress response in broiler chickens. Stress response was analyzed by the quantity of telomeric DNA, the rate of DNA damage and the expression levels of heat shock proteins (HSPs) and hydroxyl-3-methyl-glutaryl coenzyme A reductase (HMGCR) genes on tissues and blood. The telomere length and telomere shortening rates were analyzed by quantitative fluorescence in situ hybridization on the nuclei of lymphocytes and tissues. The DNA damage rate of lymphocytes was quantified by the comet assay. The expression levels of HSP70, HSP90s and HMGCR genes were measured by quantitative real-time polymerase chain reaction in lymphocytes. In results, there was no significant difference among treatments in body weight, weight gain, feed intake and mortality. The telomere shortening rate of the lymphocytes was significantly lower in the vitamin E supplemented group than the control group. The DNA damage was also decreased supplemented with vitamin C and E, as compared to the control group. The vitamin E supplemented group had a significant positive effect on the expressions of HMGCR, HSP90-${\alpha}$ and HSP90-${\beta}$ in lymphocytes, but had no significance on HSP70, as compared to the control group. We concluded that the dietary supplementation of vitamin E (100 mg/kg feed) had reduced the individual physiological stress response without stunt growth in broiler chickens.

• Journal of Korean Society on Water Environment
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• v.29 no.2
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• pp.232-238
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• 2013

Water temperature is key factor influencing growth and reproduction of fish and its increase give rise to various physiological changes including gene expression. Heat shock protein (Hsp), one of the molecular chaperones, is highly conserved throughout evolution and its expression is induced by various stressors such as temperature, oxidative, physical and chemical stresses. Here, we isolated partial cDNA clones encoding 70-kDa Hsp (Hsp70) and $\beta$-actin using reverse transcriptase-PCR (RT-PCR) from gut of Rhynchocypris kumgangensis, a Korean indigenous species and cold-water fish, and investigated expression profiles of Hsp70 under an increase of water temperature using $\beta$-actin as an internal control for RT-PCR. Cloned Hsp70 cDNA of R. kumgangensis showed homology to Ctenopharyngodon idella (96%), Hypophthalmichthys molitrix (96%), Danio rerio (93%) and Oncorhynchus mykiss (81%) Hsp70. Cloned $\beta$-actin cDNA of R. kumgangensis showed homology to D. rerio (98%), H. molitrix (97%), C. idella (97%) and O. mykiss (90%) $\beta$-actin. Both mRNA of Hsp70 and $\beta$-actin were expressed in gut, brain, and liver in R. kumgangensis. Futhermore, expression of Hsp70, in brain, was highly augmented by an increase of water temperature. These results suggest that Hsp70 mRNA expression level in brain can be used as a biological molecular marker to represent physiological stress against an increase of water temperature.

• Journal of Life Science
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• v.18 no.12
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• pp.1637-1643
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• 2008

This study has investigated whether extracellular HSP90 predisposes vascular smooth muscle cells (VSMCs) to pro-inflammatory phenotype. Exposure of rat aortic smooth muscle cells to HSP90 not only enhanced IL-6 release but also profoundly induced IL-6 transcript via promoter activation. HSP90-induced IL-6 promoter activation was suppressed by dominant-negative forms of Toll-like receptor (TLR)-4 and myeloid differentiation factor 88 (MyD88), but not by dominant-negative-forms of TLR-3 and TIR-domain-containing adapter-inducing interferon-${\beta}$ (TRIF). Curcumin, which inhibits dimerization of TLR-4, also attenuated the IL-6 induction by HSP90. Mutation at the NF-${\kappa}B$- or C/EBP-binding site in the IL-6 promoter region suppressed the promoter activation in response to HSP90. The gene delivery of $I{\kappa}B$ using recombinant adenoviruses and treatment with resveratrol, which inhibit NF-${\kappa}B$ activity, attenuated the HSP90-induced IL-6 release from VSMCs. The present study proposes that extracellular HSP90 would contribute to inflammatory reaction in the stressed vasculature by inducing IL-6 in VSMCs, and that TLR-4 and NF-${\kappa}B$ would play active roles in the process.

• Korean Journal of Poultry Science
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• v.41 no.2
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• pp.115-125
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• 2014

With Single Comb White Leghorn (WL) and Korean Native Chicken (KNC) breeds, we compared the stress response with chicken breeds that were subjected to a high stocking density. Stress response was analyzed by the quantity of telomeric DNA, the rate of DNA damage and the expression levels of heat shock proteins (HSPs) and hydroxyl-3-methyl-glutaryl coenzyme A reductase (HMGCR) genes on tissues and blood. The telomere length and telomere shortening rates were analyzed by quantitative fluorescence in situ hybridization on the nuclei of lymphocytes and tissues. The DNA damage rate of lymphocytes was quantified by the comet assay. The expression levels of HSP70, HSP90-${\alpha}$, HSP90-${\beta}$ and HMGCR genes were measured by quantitative real-time polymerase chain reaction in lymphocytes. There was no significant difference between KNC and WL in body weight, weight gain, telomere shortening rate and DNA damage rate. However, the growth rate significantly decreased in chickens raised under high stocking density conditions, as compared to the control group. The telomere-shortening rate, DNA damage and HSPs expression of the lymphocytes were significantly higher in the high stocking density group than the control. The stress condition and breeds had a significant effect on the expressions of HSP70, HSP90-${\alpha}$ and HSP90-${\beta}$ in lymphocytes, except HMGCR. The stress response of WL was higher than that of KNC, as analyzed to the expression of HSP70 and HSP90-${\alpha}$. Therefore, we concluded that the chickens which were exposed to a high stocking density had increased the individual physiological stress response regardless of breeds, and White Leghorns are more susceptible to stress condition than Korean Native Chickens.

• Journal of Marine Life Science
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• v.3 no.2
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• pp.51-58
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• 2018

Variations in water temperature are known to affect almost every part of fish physiology. The rise in water temperature due to climate change can physically damage fish. This study was conducted to evaluate the health status of the Atlantic salmon (Salmo salar) at high water temperature (20℃) than the optimum water temperature (15℃). Liver tissue exerts important metabolic functions in thermal adaptation. Therefore, liver tissue was used in this study. The evaluation method is to develop the biomarker gene using NGS RNAseq analysis and to examine the expression pattern using RT-qPCR analysis. The NGS RNAseq analysis revealed 1,366 differentially expressed genes, among which 880 genes were increase expressed and 486 genes were decrease expressed. The biomarker genes are such as heat shock protein 90 alpha (Hsp90α), heat shock protein 90 beta (Hsp90β) and cytochrome P450 1A (CYP1A). The selected genes are sensitive to changes in water temperature through NGS RNAseq analysis. Expression patterns of these genes through RT-qPCR were similar to those of NGS RNAseq analysis. The results of this study can be applied to other fish species and it is considered to be useful industrially.

• Korean Journal of Poultry Science
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• v.46 no.2
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• pp.77-86
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• 2019

This study was conducted to compare the heat stress response and production performance of chicks hatched in winter and summer. Among the 2,090 Korean native chickens examined, 1,156 hatched in winter and 934 hatched in summer. The amount of telomeric DNA, the expression of heat shock protein (HSP) genes, survival rate, egg production, and body weight were analyzed to evaluate the stress response and production performance of chickens. The results showed that the expression of HSP-70, $HSP-90{\alpha}$, and $HSP-90{\beta}$ genes in the winter-hatched chickens were significantly higher than those in the summer-hatched chickens during the growing and laying period (P<0.05). There was no significant difference in the amount of telomeric DNA between summer- and winter-hatched chickens. The survival rate was significantly higher in the summer-hatched chickens than in the winter-hatched chickens at the laying period (P<0.01). The hen-day egg production and egg weight in the summer-hatched chickens were also significantly higher than those in the winter-hatched chickens (P<0.05). In contrast, age of sexual maturity of winter-hatched chickens was significantly earlier than that of summer-hatched chickens (P<0.01). The body weights from birth to 24 weeks were significantly lighter in the summer-hatched chickens than in the winter-hatched chickens, however, it was reversed after 28 weeks (P<0.05). In conclusion, the chicks hatched in the summer are more resistant to heat stress, with better productivity than the chicks hatched in the winter. These results suggest that the chicks grown at high temperatures have greater adaptability to the thermal environment.

• Molecules and Cells
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• v.20 no.3
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• pp.378-384
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• 2005

Estrogen metabolites are carcinogenic. The comparative mitogenic activities of $17{\beta}$-estradiol (E2) and four metabolites, 2-hydroxyestradiol (2-OHE2), 4-hydroxyestradiol (4-OHE2), $16{\alpha}$-hydroxyestrone ($16{\alpha}$-OHE1) and 2-methoxyestradiol (2-ME), were determined in estrogen receptor(ER)-positive MCF-7 human breast cancer cells. Each of the E2 metabolites caused proliferation of the MCF-7 cells, but only E2 and $16{\alpha}$-OHE1 induced a greater than 20-fold increases in transcripts of the progesterone receptor (PR) gene, a classical ER-mediated gene. This suggests that the mitogenic action of E2 and $16{\alpha}$-OHE1 could result from their effects on gene expression via the ER. E2 metabolites altered the expression of E2-regulated proteins including heat shock proteins (Hsps). $16{\alpha}$-OHE1 and 2-ME as well as E2 increased levels of Hsp56, Hsp60, $Hsp90{\alpha}$ and Hsp110 transcripts, and the patterns of these inductions resembled that of PR. Hsp56 and Hsp60 protein levels were increased by all the E2 metabolites. Levels of the transcripts of 3 E2-upregulated proteins (XTP3-transactivated protein A, protein disulfide isomerase-associated 4 protein and stathmin 1) and an E2-downregulated protein (aminoacylase 1) were also affected by the E2 metabolites. These results suggest that the altered expression of Hsps (especially Hsp56 and Hsp60) by E2 metabolites such as E2, $16{\alpha}$-OHE1 and 2-ME could be closely linked to their mitogenic action.

• Molecular & Cellular Toxicology
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• v.4 no.3
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• pp.199-204
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• 2008

The bio-molecules involved in defense mechanisms can be used as efficient biomarkers for physiological changes in organisms caused by both of internal and external stress. Thus, the expression level of genes which encoding such molecules serve as critical 'early warning system' for environmental assessment as well as health diagnosis of biological organisms. In this study, Cytochrome P450, Heat shock protein 90, Ubiquitin and ${\beta}$-actin gene were isolated for the first time from a red alga Gracilaria textorii. The quantitative differential gene expression analyses of three genes, GteCYP1A, GteHsp90 and Gte-UB, were carried out in G. textorii sporophytes collected from two different localities, polluted Sujeong (Masan, Korea) and potentially unpolluted Danggeum (Daemaemuldo Is., Korea). The transcripts of all three tested genes were highly expressed in the Sujeong population. The results suggest: 1) the Sujeong site was more polluted than the Danggeum site; 2) G. textorii could be applicable to marine environment monitoring in coastal regions.

• Journal of Life Science
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• v.23 no.4
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• pp.586-594
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• 2013

Post-translational O-GlcNAc modification (O-GlcNAcylation) of serine or threonine is a new protein modulation mechanism. In contrast to the classical glycosylation, O-GlcNAcylation occurs in a one-step transfer of O-GlcNAc on both nuclear and cytoplasmic proteins. In contrast to the general consensus that O-GlcNAc is a final modification, a recent paper (J Proteome Res. 2011 10:2725-2733) showed the presence of O-GlcNAc-P on a synaptic assembly protein AP180. This finding raises a fundamental question about its prevalence. To address this question, we used proteomics to identify those proteins that were phospho-signal enriched by GlcNAc kinase (NAGK). Comparison of pDsRed2-$NAGK_{WT}$-transfected HEK293T cell extract with pDsRed2-$NAGK_{D107A}$-transfected control culture revealed 15 phospho-signal increased spots. Excluding those spots that had no detectable amount of protein expression yielded 7 spots, which were selected for ID determination. Among these, two duplicate spots (two $HSP90{\beta}$ and two ENO1 spots) were shown to be O-GlcNAcylated, two (dUTP nucleotidohydrolase mitochondrial isoform 2, glutathione S-transferase P) were not known to be involved in O-GlcNAcylation, and one (heat shock protein gp96 precursor or grp94) was a glycoprotein. The increase in the phospho-levels of O-GlcNAc by NAGK strongly indicates that these proteins are phosphorylated on O-GlcNAc. Our present data support the idea that O-GlcNAc is not a terminal modification.