• Journal of Korean Neurosurgical Society
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• v.30 no.3
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• pp.263-271
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• 2001

Objective : Glioblastomas, the most common type of primary brain tumors, are highly invasive and cause massive tissue destruction at both the tumor invading edges and in areas that are not in direct contact with glioma cells. As a result, patients with high-grade gliomas are faced with a poor prognosis. Such grim statistics emphasize the need to better understand the mechanisms that underlie glioma invasion, as these may lead to the identification of novel targets in the therapy of high grade gliomas. Protein kinase C(PKC) is a family of serine/threonine kinases and an important signal transduction enzyme that conveys signals generated by ligand-receptor interaction at the cell surface to the nucleus. PKC appears to be critical in regulating many aspects of glioma biology. The purpose of this study was to assess accurately the role of PKC in the invasion regulation of human gliomas based on hypothesis that protein kinase C(PKC) is functional in the process of glial tumor cell invasion. Method : To test this hypothesis, U-87 malignant glioma cell line intracellular PKC levels were up and down regulated and their invasiveness was tested. Intracellular PKC level was characterized using PKC activity assays. Invasion assays including barrier migration and spheroid confrontation were used to study the relationship between PKC concentration and invasiveness. Result : The cell line which were treated by PKC inhibitor tamoxifen and hypericin exhibited decreased PKC activity and decreased invasive abilities dose dependently both in matrigel invasion assay and tumor spheroid fetal rat brain aggregates(FRBA) confrontation assay. However, the cell line that was treated by PKC activator 12-O-tetradecanylphorbol-13acetate(TPA) did not exhibit increases in either PKC activity or invasive ability. Conclusion : These studies suggest that PKC may be a useful molecular target for the chemotherapy of glioblastoma and other malignancies and that a therapeutic approach based on the ability of PKC inhibitors may be helpful in preventing invasion.

• Tuberculosis and Respiratory Diseases
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• v.54 no.2
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• pp.199-209
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• 2003

Background : Unexplained weight loss, which commonly occurs in patients with chronic obstructive pulmonary disease(COPD), is important because weight loss is an independent risk factor of mortality and morbidity in these patients. Leptin is known to play an important role in regulating body weight. In addition, the tumor necrosis factor($TNF-{\alpha}$) might also play a potential role in the weight loss experienced in chronic wasting disease. The aim of this study was to determine the influence of plasma leptin and the circulating $TNF-{\alpha}$ system to the difference in the body compositions in patients with COPD. Methods : Spirometry, body composition analysis and the plasma concentrations of leptin, $TNF-{\alpha}$ and a soluble TNF receptor (STNF-R55, -R75) were measured in 31 patients with chronic bronchitis and 10 patients with emphysema. The COPD subtype was classified by the transfer coefficient of carbon monoxide, DLco/VA. Results : The circulating levels of leptin were significantly lower in those patients with emphysema($108.5{\pm}39.37pg/ml$) than those with chronic bronchitis($180.9{\pm}57.7pg/ml$). The circulating levels of sTNF-R55 were significantly higher in the emphysema patients($920.4{\pm}116.4pg/ml$) than in those with chronic bronchitis($803.2{\pm}80.8pg/ml$). There was no relationship between the circulating leptin levels and the activated TNF system in patients with chronic bronchitis and emphysema. However, the circulating leptin levels correlated well with the BMI and fat mass in both patient groups. Conclusion : These results suggest that the weight loss noted in emphysema patients may be associated with the activation of the $TNF-{\alpha}$ system rather than the plasma leptin level.

• Molecules and Cells
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• v.37 no.2
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• pp.178-186
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• 2014

Differential transcription of the clusterin (CLU) gene yields two CLU isoforms, a nuclear form (nCLU) and a secretory form (sCLU), which play crucial roles in prostate tumorigenesis. Pro-apoptotic nCLU and anti-apoptotic sCLU have opposite effects and are differentially expressed in normal and cancer cells; however, their regulatory mechanisms at the transcriptional level are not yet known. Here, we examined the transcriptional regulation of nCLU in response to hypoxia. We identified three putative hypoxia response elements (HREs) in the human CLU promoter between positions -806 and +51 bp. Using a luciferase reporter, electrophoretic gel mobility shift, and chromatin immunoprecipitation assays, we further showed that hypoxia-inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) bound directly to these sites and activated transcription. Exposure to the hypoxia-mimetic compound $CoCl_2$, incubation under 1% $O_2$ conditions, or overexpression of HIF-$1{\alpha}$ enhanced nCLU expression and induced apoptosis in human prostate cancer PC3M cells. However, LNCaP prostate cancer cells were resistant to hypoxia-induced cell death. Methylation-specific PCR analysis revealed that the CLU promoter in PC3M cells was not methylated; in contrast, the CLU promoter in LNCap cells was methylated. Co-treatment of LNCaP cells with $CoCl_2$ and a demethylating agent promoted apoptotic cell death through the induction of nCLU. We conclude that nCLU expression is regulated by direct binding of HIF-$1{\alpha}$ to HRE sites and is epigenetically controlled by methylation of its promoter region.

• Journal of Life Science
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• v.20 no.8
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• pp.1193-1200
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• 2010

The cDNA cloning and developmental profiles of the mRNA for A. pernyi arylphorin was determined. The complete A. pernyi arylphorin cDNA sequence comprised 2,234 bp (without the poly $A^+$ tail), including an open reading frame of 2,112 bp beginning with a methionine ATG at bp34. The A. pernyi arylphorin contained 704 amino acids which are highly enriched in aromatic amino acids, phenylalanine and tyrosine. The calculated molecular mass of the A. pernyi arylphorin from the ORF was 83,439 Da. The deduced amino acid sequence of A. pernyi arylphorin showed 78, 71, 62 and 64% identity with those of H. cecropia, M. sexta $\alpha$ subunit, M. sexta $\beta$ subunit and B. mori storage protein. In Northern blot analysis, the A. pernyi arylphorin mRNA only in the fat body of the 5th instar larvae was responsible for gene expression of the protein, and the synthetic activity of the mRNA was detected strongly in the early larvae, but not in the middle or late-stage larvae. In addition, a very weak signal in mRNA activity was detected in pupal stages, but this was considered to be inactive mRNA after reviewing the results of the labeling experiment of this protein.

• Journal of Life Science
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• v.28 no.4
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• pp.435-443
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• 2018

AMP-activated protein kinase (AMPK) functions as a metabolic master through regulating and restoring cellular energy balance. In skeletal muscle, AMPK increases myofibril protein degradation through the expression of muscle-specific ubiquitin ligases. Mori Folium, the leaf of Morus alba, is a traditional medicinal herb with various pharmacological functions; however, the effects associated with muscle atrophy have not been fully identified. In this study, we confirmed the effects of AMPK activation by examining the effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, on the induction of atrophy and expression of atrophy-related genes in C2C12 myotubes. We also investigated the effects of the ethanol extract of Mori Folium (EEMF) on the recovery of AICAR-induced muscle atrophy in C2C12 myotubes. It was found that exposure to AICAR resulted in the stimulation of Forkhead box O3a (FOXO3a); an up-regulation of muscle-specific ubiquitin ligases such as Muscle Atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger-1 (MuRF1), and a down-regulation of muscle-specific transcription factors, such as MyoD and myogenin; with the activation of AMPK. In addition, AICAR without cytotoxicity indicated a decrease in diameter of C2C12 myotubes. However, treatment with EEMF significantly suppressed AICAR-induced muscle atrophy of C2C12 myotubes in a dose-dependent manner as confirmed by a decrease in myotube diameter, which is associated with a reversed stimulation of FOXO3a by the inhibition of AMPK activation. These results indicate that the activation of AMPK by AICAR induces muscle atrophy, and EEMF has preeminent effects on the inhibition of AICAR-induced muscle atrophy through the AMPK signaling pathway.

• Molecules and Cells
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• v.38 no.3
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• pp.210-220
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• 2015

Athletic performance is an important criteria used for the selection of superior horses. However, little is known about exercise-related epigenetic processes in the horse. DNA methylation is a key mechanism for regulating gene expression in response to environmental changes. We carried out comparative genomic analysis of genome-wide DNA methylation profiles in the blood samples of two different thoroughbred horses before and after exercise by methylated-DNA immunoprecipitation sequencing (MeDIP-Seq). Differentially methylated regions (DMRs) in the pre-and post-exercise blood samples of superior and inferior horses were identified. Exercise altered the methylation patterns. After 30 min of exercise, 596 genes were hypomethy-lated and 715 genes were hypermethylated in the superior horse, whereas in the inferior horse, 868 genes were hypomethylated and 794 genes were hypermethylated. These genes were analyzed based on gene ontology (GO) annotations and the exercise-related pathway patterns in the two horses were compared. After exercise, gene regions related to cell division and adhesion were hypermethylated in the superior horse, whereas regions related to cell signaling and transport were hypermethylated in the inferior horse. Analysis of the distribution of methylated CpG islands confirmed the hypomethylation in the gene-body methylation regions after exercise. The methylation patterns of transposable elements also changed after exercise. Long interspersed nuclear elements (LINEs) showed abundance of DMRs. Collectively, our results serve as a basis to study exercise-based reprogramming of epigenetic traits.

• Asian Journal of Turfgrass Science
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• v.19 no.2
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• pp.103-113
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• 2005

This study was conducted to improve the green up of zoysiagrass(2. japonica) and cool-season grass($80\%$ Kentucky bluegrass+$20\%$ Perennial ryegrass) during early spring in Korea. Treatments fur zoysiagrass were control, Polyethylene film, Black screen, Black screen+polyethylene film, Green screen+polyethylene film, Polyethylene film+Black screen, Polyethylene film+Green screen, low mowing height(1.5-2cm) and homing. For cool-season grass, non-punched Polyethylene film, punched Polyethylene film treatments were included. Application dates of covering with Polyethylene film were Feb. 22, Feb. 28, March 7, and March 14. Green up was evaluated by visual color rating. The results are as follows; 1. The best method for improving green up of zoysiagrass were Polyethylene film and optimal covering day for zoysiagrass was on Feb. 22. 2. Low mowing height(1.5-2cm) and burning of zoysiagrass showed the faster greening 1$\sim$weeks before than control. .3 Non-punched Polyethylene film covering was best to improve green up of cool-season grass. More time of covering time with cool-season grass induces rapid green up.

• Journal of Plant Biotechnology
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• v.41 no.3
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• pp.146-158
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• 2014

Camelina sativa that belongs to Brassicaceae family is an emerging oilseed crop. Camelina seeds contain approximately 40% storage oils per seed dry weight, which are useful for human and animal diets and industrial applications. Microsomal delta-12 fatty acid desaturase2 (FAD2) catalyzes the conversion of oleic acid to linoleic acid. The polymorphisms of FAD2 genes are correlated with the levels of oleic acids in seed oils. Microsomal delta-12 fatty acid desaturase2 (FAD2) catalyzes the conversion of oleic acid to linoleic acid. The polymorphisms of FAD2 genes are correlated with the levels of oleic acids in seed oils. In this study, three CsFAD2 genes (CsFAD2-1, CsFAD2-2 and CsFAD2-3.1) were isolated from developing seeds of Camelina sativa (L.) cv. CAME. The nucleotide and deduced amino acid sequences of three CsFAD2 genes were compared with those from dicotyledon and monocotyledon plants including Camelina cultivars Sunesone and SRS933. Three histidine motifs (HECGH, HRRHH, and HVAHH) required for FAD activity and a hydrophobic valine or isoleucine residue, which is a SNP (single nucleotide polymorphism) marker related with enzyme activity are well conserved in three CsFAD2s. The expressions of CsFAD2-1 and CsFAD2-3.1 were ubiquitously detected in various Camelina organs, whereas the CsFAD2-2 transcripts were predominantly detected in flowers and developing seeds. The contents of oleic acids decreased, whereas the amounts of linoleic acid increased in dry seeds of transgenic fad2-2 lines expressing each CsFAD2 gene compared with fad2-2 mutant, indicating that three CsFAD2 genes are functionally active. The isolated CsFAD2 genes might be applicable in metabolic engineering of storage oils with high oleic acids in oilseed crops.

• Tuberculosis and Respiratory Diseases
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• v.52 no.5
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• pp.497-505
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• 2002

Background : INF-${\gamma}$ plays an important role in the host response to a mycobacterial infection. A complete IFN-${\gamma}$ receptor 1 deficiency is a life threatening condition because it renders patients highly susceptible to a mycobacterial infection. Several mutations in the IFN-${\gamma}$ receptor and STAT1 gene have been identified in the rare mycobacterial infections. These mutations have partial function of the IFN-${\gamma}$ receptor and similar pathologic features to clinical tuberculosis. Materials and Methods : The function of the IFN-${\gamma}$ receptor was evaluated in the patients with clinical tuberculosis. In addition, the DNA coding sequence of the IFNgR1 and STAT1 gene was also analyzed in disseminated tuberculosis patients who might have a defective IFN-${\gamma}$ receptor. Results : The cell surface expression levels of HLA-DR and CD64 in the PMBC after being stimulation with IFN-${\gamma}$ (100IU/ml, 1000IU/ml) were increased in both controls and patients. However, the rate of increase in both groups was similar. The production of TNF-${\alpha}$ in the response to stimulation with LPS was higher in the both groups ($850.7{\pm}687.8$ vs. $836.7{\pm}564.3$ pg/ml). Pretreatment with IFN-${\gamma}$ prior to LPS stimulation resulted in further increase in TNF-${\alpha}$ production between both groups ($2203.5{\pm}242.5$ vs. $2227.5{\pm}560.4$ pg/ml). However, the rate of the increase in TNF-${\alpha}$ production in the both groups was similar. The known mutations in the IFNgR1 and STAT1 coding sequences were not found in the genomic DNA of patients with disseminated tuberculosis. Conclusion : The functional and genetic defects of the IFN-${\gamma}$ receptor were not identified in clinical tuberculosis. This suggests the defective IFN-${\gamma}$ receptor that predispoe patients to a BCG or NTM infection can not alone account for the cases of clinical tuberculosis.

• Clinical and Experimental Pediatrics
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• v.53 no.2
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• pp.167-172
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• 2010

Purpose : With improved survival of extremely low birth weight infants (ELBWI), there is an increase in the incidence of necrotizing enterocolitis (NEC) requiring laparotomy, and the risk of morbidity and mortality in these ELBWI is increased. Thus, we determined the prognostic factors in ELBWI who underwent laparotomy for NEC. Methods : We retrospectively reviewed the medical records of 35 ELBWI who underwent laparotomy for NEC from January 2001 to December 2008 at Samsung Medical Center. Results : Of 480 ELBWI, 35 required laparotomy for NEC; the mortality rate was 20% (Alive group n=28, Dead group n=7). The values of preoperative score for neonatal acute physiology-II (P =0.022) and fraction of inspired oxygen (P <0.001) were significantly higher in the dead group and values of base excess (P =0.004) were significantly lower in the dead group. Values of preoperative heart rate, respiration rate, mean blood pressure, pH, $CO_2$, and potassium ion were not significantly different between the study groups. Intraoperative fluid volume was significantly higher in the alive group than in the dead group (P =0.045). Postoperative infusion rate was significantly lower in the alive group than in the dead group (P =0.022). Conclusion : Good preoperative condition, more intraoperative fluid infusion, and stable postoperative hemodynamic condition were factors associated with favorable prognosis of laparotomy for NEC in ELBWI.