• BMB Reports
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• v.53 no.11
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• pp.576-581
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• 2020

Dimethylation of the histone H3 protein at lysine residue 9 (H3K9) is mediated by euchromatin histone methyltransferase II (EHMT2) and results in transcriptional repression of target genes. Recently, chemical inhibition of EHMT2 was shown to induce various physiological outcomes, including endoplasmic reticulum stress-associated genes transcription in cancer cells. To identify genes that are transcriptionally repressed by EHMT2 during apoptosis, and cell stress responses, we screened genes that are upregulated by BIX-01294, a chemical inhibitor of EHMT2. RNA sequencing analyses revealed 77 genes that were upregulated by BIX-01294 in all four hepatic cell carcinoma (HCC) cell lines. These included genes that have been implicated in apoptosis, the unfolded protein response (UPR), and others. Among these genes, the one encoding the stress-response protein Ras-related GTPase C (RRAGC) was upregulated in all BIX-01294-treated HCC cell lines. We confirmed the regulatory roles of EHMT2 in RRAGC expression in HCC cell lines using proteomic analyses, chromatin immune precipitation (ChIP) assay, and small guide RNA-mediated loss-of-function experiments. Upregulation of RRAGC was limited by the reactive oxygen species (ROS) scavenger N-acetyl cysteine (NAC), suggesting that ROS are involved in EHMT2-mediated transcriptional regulation of stress-response genes in HCC cells. Finally, combined treatment of cells with BIX-01294 and 5-Aza-cytidine induced greater upregulation of RRAGC protein expression. These findings suggest that EHMT2 suppresses expression of the RRAGC gene in a ROS-dependent manner and imply that EHMT2 is a key regulator of stress-responsive gene expression in liver cancer cells.

• Journal of Microbiology and Biotechnology
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• v.20 no.11
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• pp.1471-1480
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• 2010

An extremely thermostable xylanase gene, xynB, from the hyperthermophilic bacterium Thermotoga maritima MSB8 was successful expressed in Kluyveromyces lactis. The response surface methodology (RSM) was also applied to optimize the medium components for the production of XynB secreted by the recombinant K. lactis. The secretion level (102 mg/l) and enzyme activity (49 U/ml) of XynB in the optimized medium (yeast extract, lactose, and urea; YLU) were much higher than those (56 mg/l, 16 U/ml) in the original medium (yeast extract, lactose, and peptone; YLP). The secretory efficiency of mature XynB was also improved when using the YLU medium. When the mRNA levels of 13 characterized secretion-related genes in the K. lactis cultured in YLP and YLU were detected using a semiquantitative RT-PCR method, the unfolded protein response (UPR)-related genes, including ero1, hac1, and kar2, were found to be up-regulated in the K. lactis cultured in YLU. Therefore, the nutrient ingredients, especially the nitrogen source, were shown to have a significant influence on the XynB secretory efficiency of the host K. lactis.

• Korean Chemical Engineering Research
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• v.50 no.3
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• pp.588-593
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• 2012

Compatibility of unsaturated polyester (UP) and low profile agent (LPA) of polystyrene (PS) have been investigated under various mixing conditions such as the ratio of UP and LPA, mixing time, mixing temperature, and input amount of 2nd UP. It was possible to obtain mixture with small particle size and low phase separation in condition of 35 g of LPA, 25 g of 1st UP input, 5 min of mixing time, 1700 rpm of mixing speed, and 45 g of 2nd UP input. It was found that compatibility of UP and LPA was very sensitive to mixing conditions. In addition, molded sample using sheet molding compound prepared by stable mixing condition appeared good properties such as low water adsorption, low shrinkage, and high gloss.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1368-1378
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• 2009

Unfolded protein response (UPR) is an important genomic response to endoplasmic reticulum (ER) stress. The ER response is characterized by changes in specific proteins, induction of ER chaperones and degradation of misfolded proteins. Also, the pathogenesis of several diseases like Alzheimer's disease, neuronal degenerative diseases, and diabetes reveal the role of ER stress as one of the causative mechanisms. Borneolum has been used for neuronal disease in oriental medicine. In the present study, the protective effect of borneolum on thapsigargin-induced apoptosis in rat C6 glial cells. Treatment with C6 glial cells with 5 uM thapsigargin caused the loss of cell viability, and morphological change, which was associated with the elevation of intracellular $Ca^{++}$ level, the increase in Grp78 and CHOP and cleavage of pro-caspase 12 Furthermore, thapsigargin induced Grp98, XBP1, and ATF4 protein expression in C6 glial cells. Borneolum reduced thapsigargin-induced apoptosis through ER pathways. In the ER pathway, borneolum attenuated thapsigargin-induced elevations in Grp78, CHOP, ATF4, and XBP1 as well as reductions in pro-caspase 12 levels. Also, our data showed that borneolum protected thapsigargin-induced cytotoxicity in astrocytes from rat (P3) brain. Taken together, our data suggest that borneolum is neuroprotective against thapsigargin-induced ER stress in C6 glial cells and astrocytes. Accordingly, borneolum may be therapeutically useful for the treatment of thapsigargin-induced apoptosis in central nervous system.

• Herbal Formula Science
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• v.26 no.4
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• pp.307-318
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• 2018

Objectives : Endoplasmic reticulum (ER) stress designates cellular responses to the accumulation of misfolded and unfolded proteins in ER, which is related to a variety of liver diseases. Present study investigated the inhibitory effects of Litsea japonica flesh water extract (LJE) aganist ER stress. Methods : After HepG2 cells were pretreated with LJE and subsequently exposed to tunicamycin (Tm) or thapsigargin (Tg), expression of C/EBP homologous protein (CHOP), glucose regulated protein 78 kDa (GRP78), asparagine synthetase (ASNS), and endoplasmic reticulum DnaJ homologue 4 (ERDJ4) were determined by immunoblot and real-time PCR analysis. Three canonical signaling pathways in response to ER stress were examined to explore molecular mechanisms involved. Results : Pretreatment of 1 mg/mL LJE inhibited Tm- or Tg-induced CHOP expression, while L. japonica fruit water extract did not. In addition, LJE decreased the levels of GRP78, ASNS, and ERDJ4 mRNA by Tm. Moreover, phosphorylations of eukaryotic translation initiation factor $2{\alpha}$ and inositol-requiring enzyme 1, expression of nuclear form of activating transcription factor $6{\alpha}$, and transactivation of ER stress response element- and unfolded protein response element-harboring luciferase activities were inhibited by LJE pretreatment. Conclusions : Present results suggest that LJE would be a candidate to prevent or treat ER stress-mediated liver injuries.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.2
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• pp.95-102
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• 2019

Endoplasmic reticulum (ER) stress is mediated by disturbance of $Ca^{2+}$ homeostasis. The store-operated calcium (SOC) channel is the primary $Ca^{2+}$ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on $Ca^{2+}$ influx in human umbilical vein endothelial cells (HUVECs) were observed with the fluorescent probe Fluo-4 AM. The effect of tunicamycin on the expression of the unfolded protein response (UPR)-related proteins BiP and CHOP was assayed by western blotting with or without inhibition of Orai1. Tunicamycin induced endothelial dysfunction by activating ER stress. Orai1 expression and the influx of extracellular $Ca^{2+}$ in HUVECs were both upregulated during ER stress. The SOC channel inhibitor SKF96365 reversed tunicamycin-induced endothelial cell dysfunction by inhibiting ER stress. Regulation of tunicamycin-induced ER stress by Orai1 indicates that modification of Orai1 activity may have therapeutic value for conditions with ER stress-induced endothelial dysfunction.

• Molecules and Cells
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• v.47 no.1
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• pp.100004.1-100004.11
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• 2024

Insulin is essential for maintaining normoglycemia and is predominantly secreted in response to glucose stimulation by β-cells. Incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, also stimulate insulin secretion. However, as obesity and type 2 diabetes worsen, glucose-dependent insulinotropic polypeptide loses its insulinotropic efficacy, whereas GLP-1 receptor (GLP-1R) agonists continue to be effective owing to its signaling switch from Gs to Gq. Herein, we demonstrated that endoplasmic reticulum (ER) stress induced a transition from Gs to Gq in GLP-1R signaling in mouse islets. Intriguingly, chemical chaperones known to alleviate ER stress, such as 4-PBA and TUDCA, enforced GLP-1R's Gq utilization rather than reversing GLP-1R's signaling switch induced by ER stress or obese and diabetic conditions. In addition, the activation of X-box binding protein 1 (XBP1) or activating transcription factor 6 (ATF6), 2 key ER stress-associated signaling (unfolded protein response) factors, promoted Gs utilization in GLP-1R signaling, whereas Gq employment by ER stress was unaffected by XBP1 or ATF6 activation. Our study revealed that ER stress and its associated signaling events alter GLP-1R's signaling, which can be used in type 2 diabetes treatment.

• Journal of Life Science
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• v.34 no.2
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• pp.113-121
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• 2024

Endoplasmic reticulum (ER) stress responses are markedly induced during toxic responses caused by various chemical substances, including difenoconazole, but no research has been conducted on 1,2,3-trichloropropane (TCP), a chemical that is generally used in agriculture and industry, which induces hepatotoxicity. Therefore, in this study, the changes in indicators for hepatotoxicity, apoptosis, and ER stress were analyzed in TCP-treated Sprague Dawley (SD) rats to study the regulatory mechanism of ER stress during the hepatotoxicity. The TCP-treated group decreased in body weight and dietary intake compared to the vehicle-treated group, and necrosis and vacuolation increased significantly in liver histology. In addition, the expression of apoptosis-related factors, including Bax/Bcl-2 and cleaved caspase (Cas)-3/Cas-3 increased significantly in the TCP-treated group compared to the vehicle-treated group. In the analysis of ER stress response indicators, the expression of C/EBP homologous protein (CHOP), phospho-eukaryotic translation initiation factor 2 alpha subunit (eIF2α), and phospho-inositol-requiring enzyme 1α (IRE1α) increased only in the TCP100-treated group and decreased in the TCP200-treated group. However, the transcriptions of growth arrest and DNA damage-34 (GADD34) increased in the TCP200-treated group, while Spliced X-box binding protein-1 (XBP1s) and unspliced XBP1(XBP1u) decreased in the same group. These results suggest that the ER stress response is successfully triggered during the hepatotoxicity induced by TCP treatment through the alternative regulation of the unfolded-protein response (UPR) pathway.

• Korean Journal of Environment and Ecology
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• v.23 no.1
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• pp.41-49
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• 2009

This research conducted a survey on the feeding crane's size, formation and distribution distance subsequent to road pattern and feeding flock's size during the wintering season eight times at the Cheolwon basin in Korea from December 2005 until February 2006. The survey results are as follows: First, the feeding flocks of the Red-crowned and White-naped Crane were found to mainly consist of two to four individuals. Mono-specific feeding flocks were more identified than hetero-specific feeding flocks in both Red-crowned and White-naped Cranes. There existed a significant difference in the ratio by size between the feeding Red-crowned and White-naped Cranes. The crane's average distribution distance from the paved road was much farther than from the unpaved road, paved farm road and unpaved farm road. In case of the white-naped crane, there was a difference in its distance length from between the road and farm road and there existed a significant difference only in the paved road in the distance length by road pattern between these two bird species[Red-crowned and White-naped Crane]. Such a result indicates that crane species don't prefer the road with frequent vehicular traffic to the road with low vehicular traffic. 5 or more individuals of feeding flocks of the Red-crowned Crane were located at a farther distance length from the paved road comparing to less than 5 individuals of the whole feeding flocks and less than 5 individual feeding flocks. 5 or more individuals of feeding flocks of the White-naped Crane were located at a farther distance length from the paved road, paved farm road and unpaved farm road than less than 5 individuals of feeding flocks of the White-naped Crane; however, there existed no difference in distance length subsequent to their group size. Conclusively, it was found out that the flocks with a larger size were more greatly affected by interrupting factors. Considering such results, there seems to be a more relation to the fact that larger size feeding flocks of crane species have a higher efficiency in the lookout for their surroundings.