• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.593-598
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• 2017

The $Na^+/H^+$ exchanger-1 (NHE-1) is a ubiquitously expressed pH-regulatory membrane protein that functions in the brain, heart, and other organs. It is increased by intracellular acidosis through the interaction of intracellular $H^+$ with an allosteric modifier site in the transport domain. In the previous study, we reported that glutamate-induced NHE-1 phosphorylation mediated by activation of protein kinase C-${\beta}$ (PKC-${\beta}$) in cultured neuron cells via extracellular signal-regulated kinases (ERK)/p90 ribosomal s6 kinases (p90RSK) pathway results in NHE-1 activation. However, whether glutamate stimulates NHE-1 activity solely by the allosteric mechanism remains elusive. Cultured primary cortical neuronal cells were subjected to intracellular acidosis by exposure to $100{\mu}M$ glutamate or 20 mM $NH_4Cl$. After the desired duration of intracellular acidosis, the phosphorylation and activation of PKC-${\beta}$, ERK1/2 and p90RSK were determined by Western blotting. We investigated whether the duration of intracellular acidosis is controlled by glutamate exposure time. The NHE-1 activation increased while intracellular acidosis sustained for >3 min. To determine if sustained intracellular acidosis induced NHE-1 phosphorylation, we examined phosphorylation of NHE-1 induced by intracellular acidosis by transient exposure to $NH_4Cl$. Sustained intracellular acidosis led to activation and phosphorylation of NHE-1. In addition, sustained intracellular acidosis also activated the PKC-${\beta}$, ERK1/2, and p90RSK in neuronal cells. We conclude that glutamate stimulates NHE-1 activity through sustained intracellular acidosis, which mediates NHE-1 phosphorylation regulated by PKC-${\beta}$/ERK1/2/p90RSK pathway in neuronal cells.

• Molecular & Cellular Toxicology
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• v.2 no.2
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• pp.75-80
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• 2006

Biomarkers identify various stages and interactions on the pathway from exposure to disease. The three categories of biomarkers are those measuring susceptibility, exposure and effect. Susceptibility biomarkers are identifiable genetic variations affecting absorption, metabolism or response to environmental agents. Biomarkers of exposure indicate the amount of a foreign compound that is absorbed into the body. Biological measurements performed on human tissues are vastly expanding the capabilities of classical epidemiology, which has relied primarily on estimates of human exposure derived form chemical levels in the air, water, and other exposure routes. Biomarkers of exposure indicate the amount of a foreign compound that is absorbed into the body. Biological measurements performed on human tissues are vastly expanding the capabilities of classical epidemiology, which has relied primarily on estimates of human exposure derived form chemical levels in the air, water, and other exposure routes. The biomarker response is typical of chemical pollution by specific classes of compound, such as (i) heavy metals (mercury, cadmium, lead, zinc), responsible for the induction of metallothionein synthesis, and (ii) organochlorinated pollutants (PCBs, dioxins, DDT congeners) and polycyclic aromatic hydrocarbons (PAHs), which induce the mixed function oxygenase (MFO) involved in their bio transformations and elimination. Currently genomic researches are developed in human cDNA clone subarrays oriented toward the expression of genes involved in responses to xenobiotic metabolizing enzymes, cell cycle components, oncogenes, tumor suppressor genes, DNA repair genes, estrogen-responsive genes, oxidative stress genes, and genes known to be involved in apoptotic cell death. Several research laboratories in Korea for kicking off these Environmental Genomics were summarized.

• Journal of Soil and Groundwater Environment
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• v.29 no.3
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• pp.14-22
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• 2024

This study established risk-based fluoride soil contamination standards according to the Korean Soil Contaminant Risk Assessment Guidelines (SRAG). Ten exposure scenarios were evaluated, broadly categorized into Scenario 1, which used the default parameters from the current SRAG, and Scenario 2, which used the latest exposure factors and bio-concentration factors. Fluoride soil standards corresponding to a total hazard index (HI) of 1.0 were determined for each scenario. For children in agricultural areas, the derived risk-based soil fluoride standard was 70 mg/kg for Scenario 1 and 27 mg/kg for Scenario 2. In industrial areas, the risk-based fluoride soil standard was 2200 mg/kg in Scenario 1 and 2300 mg/kg in Scenario 2. This study clearly demonstrated that the crop ingestion exposure pathway exerted predominent influence on the estimated human health risk standards. Additionally, using the Added Risk Approach and considering soil background concentrations, the total fluoride soil standards for residential areas ranged from 232 mg/kg to 444 mg/kg, while the standards for industrial areas ranged from 2405 mg/kg to 2674 mg/kg.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.2
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• pp.179-188
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• 2017

With the explosive increase in exposure to radiofrequency electromagnetic fields (RF-EMF) emitted by mobile phones, public concerns have grown over the last few decades with regard to the potential effects of EMF exposure on the nervous system in the brain. Many researchers have suggested that RF-EMFs can effect diverse neuronal alterations in the brain, thereby affecting neuronal functions as well as behavior. Previously, we showed that long-term exposure to 835 MHz RF-EMF induces autophagy in the mice brain. In this study, we explore whether shortterm exposure to RF-EMF leads to the autophagy pathway in the cerebral cortex and brainstem at 835 MHz with a specific absorption rate (SAR) of 4.0 W/kg for 4 weeks. Increased levels of autophagy genes and proteins such as LC3B-II and Beclin1 were demonstrated and the accumulation of autophagosomes and autolysosomes was observed in cortical neurons whereas apoptosis pathways were up-regulated in the brainstem but not in the cortex following 4 weeks of RF exposure. Taken together, the present study indicates that monthly exposure to RF-EMF induces autophagy in the cerebral cortex and suggests that autophagic degradation in cortical neurons against a stress of 835 MHz RF during 4 weeks could correspond to adaptation to the RF stress environment. However, activation of apoptosis rather than autophagy in the brainstem is suggesting the differential responses to the RF-EMF stresses in the brain system.

• Journal of Environmental Health Sciences
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• v.48 no.3
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• pp.151-158
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• 2022

Background: Chemical emissions in the environment have rapidly increased with the accelerated industrialization taking place in recent decades. Residents of industrial complexes are concerned about the health risks posed by chemical exposure. Objectives: This study was performed to suggest modeling methods that take into account multimedia and multi-pathways in human exposure and risk assessment. Methods: The concentration of benzene emitted at industrial complexes in Daesan, South Korea and the exposure of local residents was estimated using the Caltox model. The amount of human exposure based on inhalation rate was stochastically predicted for various activity stages such as resting, normal walking, and fast walking. Results: The coefficient of determination (R²) for the CalTOX model efficiency was 0.9676 and the root-mean-square error (RMSE) was 0.0035, indicating good agreement between predictions and measurements. However, the efficiency index (EI) appeared to be a negative value at -1094.4997. This can be explained as the atmospheric concentration being calculated only from the emissions from industrial facilities in the study area. In the human exposure assessment, the higher the inhalation rate percentile value, the higher the inhalation rate and lifetime average daily dose (LADD) at each activity step. Conclusions: Prediction using the Caltox model might be appropriate for comparing with actual measurements. The LADD of females was higher ratio with an increase in inhalation rate than those of males. This finding would imply that females may be more susceptible to benzene as their inhalation rate increases.

• Development and Reproduction
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• v.24 no.2
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• pp.113-123
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• 2020

Metformin has been widely used as an antidiabetic drug, and reported to inhibit cell proliferation in many cancers including non-small cell lung cancer (NSCLC). In NSCLC cells, metformin suppresses PI3K/AKT/mTOR signaling pathway, but effect of metformin on RAS/RAF/MEK/ERK signaling pathway is controversial; several studies showed the inhibition of ERK activity, while others demonstrated the activation of ERK in response to metformin exposure. Metformin-induced activation of ERK is therapeutically important, since metformin could enhance cell proliferation through RAS/RAF/MEK/ERK pathway and lead to impairment of its anticancer activity suppressing PI3K/AKT/mTOR pathway, requiring blockade of both signaling pathways for more efficient antitumor effect. The present study tested the combination therapy of metformin and trametinib by monitoring the alterations of regulatory effector proteins of cell signaling pathways and the effect of the combination on cell viability in NCI-H2087 NSCLC cells with NRAS and BRAF mutations. We show that metformin alone blocks PI3K/AKT/mTOR signaling pathway but induces the activation and phosphorylation of ERK. The combination therapy synergistically decreased cell viability in treatment with low doses of two drugs, while it gave antagonistic effect with high doses. These findings suggest that the efficacy of metformin and trametinib combination therapy may depend on the alteration of ERK activity induced by metformin and specific cellular context of cancer cells.

• Journal of the Korean Institute of Electrical and Electronic Material Engineers
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• v.22 no.12
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• pp.1014-1017
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• 2009

In this study, we studied the nature of thin films formed by holographic photodoping chalcogenide thin films with for use in programmable metallization cell devices(PMC), a type of ReRAM. We formatted straight conduction pathway from the internal interferences of the diffraction gratings which is builded by the holographic lithography method. We investigated the resistance change of solid-electrolyte chalcogenide thin films varied in the applied voltage bias direction from about $1\;M{\Omega}$ to several hundreds of $\Omega$. The switching characteristics of the devices applied holographic lithography method was more improved than ultraviolet exposure condition. As a result of improved resistance change effects, we can analogize that the diffraction gratings is a kind of pattern for straight conduction pathway formation inside the chalcogenide thin films.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.78-78
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• 2002

Microsomal epoxide hydrolase (mEH), an epoxide detoxifying enzyme and putative cell surface autoantigen, is inducible by xenobiotics and by certain pathophysiological conditions. The present study was designed to determine mEH expression in H4IIE cells during cell death initiated by sulfur amino acid deprivation (SAAD) and to identify the signaling pathway for the enzyme induction.(omitted)

• Journal of Radiation Protection and Research
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• v.15 no.2
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• pp.67-74
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• 1990

A methodology for calculating acceptable levels of contamination of radionuclides in soil for unrestricted use was described. Pathways of exposure include direct radiation from ground surfaces, ingestion of contaminated food and inhalation of resuspended radionuclides. Results calculated using site-specific data for Korean environment were discussed and compared with those estimated by other guidelines.

• Molecules and Cells
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• v.26 no.4
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• pp.344-349
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• 2008

5-Fluorouracil (5-FU), a pyrimidine antagonist, has a long history in cancer treatment. The targeted pyrimidine biosynthesis pathway includes dihydropyrimidine dehydrogenase (DPD), which converts 5-FU to an inactive metabolite, and thymidylate synthase (TS), which is a major target of 5-FU. Using Caenorhabditis elegans as a model system to study the functional and resistance mechanisms of anti-cancer drugs, we examined these two genes in order to determine the extent of molecular conservation between C. elegans and humans. Overexpression of the worm DPD and TS homologs (DPYD-1 and Y110A7A.4, respectively) suppressed germ cell death following 5-FU exposure. In addition, DPYD-1 depletion by RNAi resulted in 5-FU sensitivity, while treatment with Y110A7A.4 RNAi and 5-FU resulted in similar patterns of embryonic death. Thus, the pathway of 5-FU function appears to be highly conserved between C. elegans and humans at the molecular level.