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Biomedical subjects

Ju-Young Kim

Publications and source records attributed to Ju-Young Kim.

10 recordsLinked to original sources
PubMed2006

Glucose-deprived HT-29 human colon carcinoma cells are sensitive to verrucosidin as a GRP78 down-regulator.

Glucose deprivation, a feature of poorly vascularized solid tumors, activates the unfolded protein response (UPR) which is a stress-signaling pathway in tumor cells that is associated with the molecular chaperone GRP78 and induction of GRP78 has been shown to protect them against programmed cell death. Thus, targeting glucose-deprived conditions may be a novel strategy in anticancer drug development. Based on that, we established a novel screening program for chaperone modulators that preferentially cytotoxic activity in cancer cells under glucose-deprived conditions. During the course of our screening system, we recently isolated an active compound, 326-2, from Penicillium verrucosum var. cyclopium and identified it as a down-regulator of the grp78 gene. As expected, 326-2 inhibited the expression of the GRP78 promoter under glucose-deprived conditions in a dose-dependent manner with an IC(50) value of 50nM. Furthermore, 326-2 was identified as verrucosidin, a pyrone-type polyketide, by ESI-MS analyses and various NMR spectroscopic methods. We found that verrucosidin prevents UPR-induced expression of protein, such as GRP78, whose expression is induced by glucose-deprived or by 2-deoxyglucose; this effect is not seen under normal growth conditions. The GRP78-inhibitory action of verrucosidin was dependent on strict hypoglycemic conditions and resulted in selective cell death of glucose-deprived HT-29 human colon cancer cells.

Cell Survival↗
PubMed2005

Identification of regulatory polymorphisms in the TNF-TNF receptor superfamily.

The tumor necrosis factor and TNF receptor (TNF-TNFR) superfamily plays very important roles in the pathogenesis of many immune-mediated diseases. Regulation of TNF-TNFR superfamily gene expression influences many aspects of the pathology associated with these diseases. In order to investigate genetic variations in the regulatory regions of the TNF-TNFR superfamily genes, promoter regions were screened by sequencing DNA samples from 24 unrelated Korean individuals. We identified a total of 68 single-nucleotide polymorphisms (SNPs) in the regulatory regions of the known TNF-TNFR superfamily genes, including 50 SNPs in the promoter regions, 16 SNPs in the 5'-UTR regions, and two SNPs in the coding regions of these genes. Among the 68 SNPs identified in this study, 25 SNPs were novel SNPs. Interestingly, the sequence alteration created by 11 SNPs completely abolished putative transcription factor binding sites in these alleles. These results suggest that these SNP sites can regulate gene expression by controlling the binding of transcription factors. The identification of function-altering SNPs in the promoter regions of the TNF-TNFR superfamily will facilitate efforts to understand the association of TNF-TNFR superfamily genes with several immune-mediated human diseases.

Binding Sites↗
PubMed2004

Comparison of amphiphilic polyurethane nanoparticles to nonionic surfactants for flushing phenanthrene from soil.

Amphiphilic polyurethane (APU) nanoparticles were synthesized through crosslinking polymerization of nano-aggregates of urethane acrylate nonionomer (UAN). The efficiency of in situ extraction of sorbed phenanthrene from aquifer material was tested using soil columns and compared with that of surfactants such as Triton X-100, Brij 30, and Tween 80. The extraction efficiency of those washing materials strongly depended on their concentration, flow rate, and the degree of sorption within soil column. That is, the extraction efficiency increased with the decrease of flow rate and the degree of sorption and the increase of the concentration. Even though the surfactants are superior to APU nanoparticles at solubilizing phenanthrene, at the same flow rate (0.02 mL/min) and concentration (4000 mg/L), the effectiveness of in situ soil washing of APU nanoparticles was about two times higher than those of surfactants. This is because, at the lower flow rates, the degree of sorption of APU nanoparticles was lower than that of surfactants, owing to the chemically crosslinked nature of APU nanoparticles.

Adsorption↗
PubMed2004

Engineered polymeric nanoparticles for soil remediation.

Hydrophobic organic groundwater contaminants, such as polynuclear aromatic hydrocarbons (PAHs), sorb strongly to soils and are difficult to remove. We report here on the synthesis of amphiphilic polyurethane (APU) nanoparticles for use in remediation of soil contaminated with PAHs. The particles are made of polyurethane acrylate anionomer (UAA) or poly(ethylene glycol)-modified urethane acrylate (PMUA) precursor chains that can be emulsified and cross-linked in water. The resulting particles are of colloidal size (17-97 nm as measured by dynamic light scattering). APU particles have the ability to enhance PAH desorption and transport in a manner comparable to that of surfactant micelles, but unlike the surface-active components of micelles, the individual cross-linked precursor chains in APU particles are not free to sorb to the soil surface. Thus, the APU particles are stable independent of their concentration in the aqueous phase. In this paper we show that APU particles can be engineered to achieve desired properties. Our experimental results show that the APU particles can be designed to have hydrophobic interior regions that confer a high affinity for phenanthrene (PHEN) and hydrophilic surfaces that promote particle mobility in soil. The affinity of APU particles for contaminants such as PHEN can be controlled by changing the size of the hydrophobic segment used in the chain synthesis. The mobility of colloidal APU suspensions in soil is controlled by the charge density or the size of the pendent water-soluble chains that reside on the particle surface. Exemplary results are provided illustrating the influence of alternative APU particle formulations with respect to their efficacy for contaminant removal. The ability to control particle properties offers the potential to produce different nanoparticles optimized for varying contaminant types and soil conditions.

Engineering↗
PubMed2004

IL-17 induces production of IL-6 and IL-8 in rheumatoid arthritis synovial fibroblasts via NF-kappaB- and PI3-kinase/Akt-dependent pathways.

Recent studies of the pathogenesis of rheumatoid arthritis (RA) have revealed that both synovial fibroblasts and T cells participate in the perpetuation of joint inflammation as dynamic partners in a mutual activation feedback, via secretion of cytokines and chemokines that stimulate each other. In this study, we investigated the role of IL-17, a major Th1 cytokine produced by activated T cells, in the activation of RA synovial fibroblasts. Transcripts of IL-17R (IL-17 receptor) and IL-17RB (IL-17 receptor B) were present in fibroblast-like synoviocytes (FLS) of RA patients. IL-17R responded with increased expression upon in vitro stimulation with IL-17, while the level of IL-17RB did not change. IL-17 enhanced the production of IL-6 and IL-8 in FLS, as previously shown, but did not affect the synthesis of IL-15. IL-17 appears to be a stronger inducer of IL-6 and IL-8 than IL-15, and even exerted activation comparable to that of IL-1beta in RA FLS. IL-17-mediated induction of IL-6 and IL-8 was transduced via activation of phosphatidylinositol 3-kinase/Akt and NF-kappaB, while CD40 ligation and p38 MAPK (mitogen-activated protein kinase) are not likely to partake in the process. Together these results suggest that IL-17 is capable of more than accessory roles in the activation of RA FLS and provide grounds for targeting IL-17-associated pathways in therapeutic modulation of arthritis inflammation.

Arthritis, Rheumatoid↗
PubMed2004

The MCP-1 promoter -2518 polymorphism in Behcet's disease: correlation between allele types, MCP-1 production and clinical symptoms among Korean patients.

OBJECTIVE: To compare the G vs. A variation at the MCP-1 promoter -2518 position among normal Koreans and Behcet patients, and to investigate possible association of this polymorphism with disease pathogenesis. METHODS: The allele type of -2518 polymorphism was determined by restriction fragment length polymorphism of Pvu II. The level of MCP-1 in serum and culture supernatent was measured by sandwich ELISA. RESULTS: The average serum level of MCP-1 in Behcet patients was 2.37 times higher than in normal controls. The serum MCP-1 concentration was higher in G-allele carriers than in AA homozygotes, and symptoms accompanying graver cases of Behcet's disease, such as gastrointestinal inflammation and uveitis, were more frequent in patients with the G-allele. However, the frequency of G-allele in patient group was not higher than that in healthy Koreans, probably due to the dominance of G-allele in general Korean population. When stimulated in vitro with IL-1beta and LPS, the mononuclear cells from patients carrying the G-allele showed a steeper increase in MCP-1 production than the boost observed in AA homozygotes. CONCLUSION: Although the allele frequency of MCP-1 promoter -2518 polymorphism is not likely to be the reason for the elevated serum MCP-1 level in Korean patients with Behcet's disease, it is possible that proinflammatory factors induced in patients' serum cause stronger activation of MCP-1 expression from the G-type promoter, as well as increased incidence of uveitis and gastric ulcer, among carriers of the G-allele.

Alleles↗
PubMed2003

Distribution of phenanthrene between soil and an aqueous phase in the presence of anionic micelle-like amphiphilic polyurethane particles.

Sorption of micelle-like amphiphilic polyurethane (APU) particles to soil was studied and compared to that of a model anionic surfactant, sodium dodecyl sulfate (SDS). Three types of APU particles with different hydrophobicity were synthesized from urethane acrylate anionomers (UAA) and used in this study. Due to the chemically cross-linked structure, APU exhibited less sorption to the soil than SDS and a greater reduction in the sorption of phenanthrene, a model soil contaminant, to the soil was observed in the presence of APU than SDS even though the solubility of phenanthrene was higher in the presence of SDS than APU. A mathematical model was developed to describe the phenanthrene distribution between soil and an aqueous phase containing APU particles. The sorption of phenanthrene to the test soil could be well described by Linear isotherm. APU sorption to the soil was successfully described by Langmuir and Freundlich isotherms. The partition of phenanthrene between water and APU were successfully explained with a single partition coefficient. The model, which accounts for the limited solubilization of phenanthrene in sorbed APU particles, successfully described the experimental data for the distribution of phenanthrene between the soil and the aqueous phase in the presence of APU.

Adsorption↗
PubMed2003

Effect of amphiphilic polyurethane nanoparticles on sorption-desorption of phenanthrene in aquifer material.

Micelle-like amphiphilic nano-sized polyurethane (APU) nanoparticles were synthesized via chemical cross-linking reaction of nano-aggregates of urethane acrylate nonionomer (UAN) chain and were tested for extraction efficiency of sorbed phenanthrene from aquifer material. Even though the solubilizing performance and interfacial activity of APU nanoparticles were inferior to that of Triton X-100, in the low concentration region, APU nanoparticles could effectively reduce phenanthrene sorption on the aquifer material and extracted sorbed phenanthrene from the aquifer material, whereas Triton X-100 could not extract sorbed phenanthrene and rather increased phenanthrene sorption onto the aquifer materials. At higher concentrations, APU nanoparticles and Triton X-100 had almost the same soil washing effectiveness. This interesting result is mainly due to a lower degree of sorption of APU nanoparticles onto the aquifer material. The sorption of APU nanoparticles onto aquifer sand is largely hindered by their chemically cross-linked nature, resulting in better soil-washing performance of APU nanoparticles than Triton X-100.

Adsorption↗
PubMed2003

Cyclic AMP induces activation of extracellular signal-regulated kinases in HL-60 cells: role in cAMP-induced differentiation.

It is well known that elevated intracellular cAMP induces growth arrest and the differentiation of HL-60 cells to neutrophil-like cells. The present study was designed to assess the regulation of the extracellular signal-regulated kinase (ERK) pathway by cAMP and its association with differentiation in HL-60 cells. We found that 8-bromoadenosine-3',5'-cyclic-monophosphate (8Br-cAMP)-induced the activation of ERK and mitogen-activated protein kinase (MEK), but inhibited B-Raf kinase via a protein kinase A (PKA)-mediated mechanism. Prolonged exposure to 8Br-cAMP increased the phorbol 12-myristate 13-acetate (TPA)-stimulated superoxide generation and CD14 expression that characterize the differentiation phenotype, which was blocked by MEK-1 inhibitor. These data suggest that cAMP-induced ERK activation is essential for the differentiation of HL-60 cells, independently of B-Raf.

8-Bromo Cyclic Adenosine Monophosphate↗