• Journal of Life Science
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• v.26 no.1
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• pp.8-16
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• 2016

Reactive oxygen species (ROS), at appropriate concentrations, mediate various normal cellular functions, including defense against pathogens, signal transduction, cellular growth, and gene expression. A recent study demonstrated that ROS and ROS-generating NADPH oxidase (Nox) are important in self-renewal and neuronal differentiation of subventricular zone (SVZ) neural stem cells in adult mouse brains. In this study, we found that endogenous ROS were detected in SVZ neural stem cells cultured from postnatal mouse brains. Nox4 was predominantly expressed in cultured cells, while the levels of the Nox1 and Nox2 transcripts were very low. In addition, the Nox4 gene was highly upregulated (by up to 10-fold) during neuronal differentiation. Immunocytochemical analysis detected the Nox4 protein mainly in neurons positive for the neuronal specific tubulin Tuj1. After differentiation, endogenous ROS were detected exclusively in neuron-like cells with processes. In addition, perturbation of the cellular redox state with N-acetyl cysteine, a ROS scavenger, during neuronal differentiation greatly inhibited neurogenesis. Lastly, knockdown of Nox4 using short hairpin RNA decreased neurogenesis. These findings suggest that Nox4 may be a major ROS-generating enzyme in postnatal SVZ neural stem cells, and Nox4-mediated ROS generation may be important in their neuronal differentiation.

• Molecules and Cells
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• v.41 no.5
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• pp.454-464
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• 2018

Crosstalk between G-protein signaling and glutamatergic transmission within the brain reward circuits is critical for long-term emotional effects (depression and anxiety), cravings, and negative withdrawal symptoms associated with opioid addiction. A previous study showed that Regulator of G-protein signaling 4 (RGS4) may be implicated in opiate action in the nucleus accumbens (NAc). However, the mechanism of the NAc-specific RGS4 actions that induce the behavioral responses to opiates remains largely unknown. The present study used a short hairpin RNA (shRNA)-mediated knock-down of RGS4 in the NAc of the mouse brain to investigate the relationship between the activation of ionotropic glutamate receptors and RGS4 in the NAc during morphine reward. Additionally, the shRNA-mediated RGS4 knock-down was implemented in NAc/striatal primary-cultured neurons to investigate the role that striatal neurons have in the morphine-induced activation of ionotropic glutamate receptors. The results of this study show that the NAc-specific knock-down of RGS4 significantly increased the behaviors associated with morphine and did so by phosphorylation of the GluR1 (Ser831) and NR2A (Tyr1325) glutamate receptors in the NAc. Furthermore, the knock-down of RGS4 enhanced the phosphorylation of the GluR1 and NR2A glutamate receptors in the primary NAc/striatal neurons during spontaneous morphine withdrawal. These findings show a novel molecular mechanism of RGS4 in glutamatergic transmission that underlies the negative symptoms associated with morphine administration.

• Molecules and Cells
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• v.44 no.3
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• pp.146-159
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• 2021

DNA methylation, and consequent down-regulation, of tumour suppressor genes occurs in response to epigenetic stimuli during cancer development. Similarly, human oncoviruses, including human papillomavirus (HPV), up-regulate and augment DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities, thereby decreasing tumour suppressor genes (TSGs) expression. Ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), an epigenetic regulator of DNA methylation, is overexpressed in HPV-induced cervical cancers. Here, we investigated the role of UHRF1 in cervical cancer by knocking down its expression in HeLa cells using lentiviral-encoded short hairpin (sh)RNA and performing cDNA microarrays. We detected significantly elevated expression of thioredoxin-interacting protein (TXNIP), a known TSG, in UHRF1-knockdown cells, and this gene is hypermethylated in cervical cancer tissue and cell lines, as indicated by whole-genome methylation analysis. Up-regulation of UHRF1 and decreased TXNIP were further detected in cervical cancer by western blot and immunohistochemistry and confirmed by Oncomine database analysis. Using chromatin immunoprecipitation, we identified the inverted CCAAT domain-containing UHRF1-binding site in the TXNIP promoter and demonstrated UHRF1 knockdown decreases UHRF1 promoter binding and enhances TXNIP expression through demethylation of this region. TXNIP promoter CpG methylation was further confirmed in cervical cancer tissue by pyrosequencing and methylation-specific polymerase chain reaction. Critically, down-regulation of UHRF1 by siRNA or UHRF1 antagonist (thymoquinone) induces cell cycle arrest and apoptosis, and ubiquitin-specific protease 7 (USP7), which stabilises and promotes UHRF1 function, is increased by HPV viral protein E6/E7 overexpression. These results indicate HPV might induce carcinogenesis through UHRF1-mediated TXNIP promoter methylation, thus suggesting a possible link between CpG methylation and cervical cancer.

• Journal of the Korean Institute of Traditional Landscape Architecture
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• v.34 no.1
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• pp.71-82
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• 2016

Through literature review and on-site survey of Gimcheon Bangcho pavilion(芳草亭), the features of garden design(庭園意匠) including geographic conditions, landscape modeling of Nujeong(樓亭) and Jidang(池塘, Pond), and scenic interpretations in Nujeong Jeiyoung poetry(樓亭題詠詩) have been carefully researched and the findings are presented below. Bangcho pavilion is located in a village called Wonteomaeul, which belongs to the feng shui state of golden hairpin and floating lotus. It has long been the cultural hub of communication and social interactions among the villagers. The Head House of Jeongyanggong(靖襄公宗宅), the main house(本第) of the Yeonan Yi Clan(延安李氏), is about 150m away from Bangcho pavilion, an artistic space whose landscape modeling is of the form called Nujeong. The name 'Bangcho' reflects the noble man(君子)'s determination: "I yearn for the place where honey parrots fly and the fragrant grass grow." From the two story structure of the pavilion where there is an additional floor installed to the central ondol room by a four-sided subdivision door, one can detect the aspiration of the men for pursuing an open view. One can also observe the efforts in designing the room to be used for multiple purposes from a private place to an office for periodic publication of a family lineage document called "Garyejunghae(家禮增解)". Bangcho pavilion's main sight of interest is Mrs Choi's Pond(崔氏潭), the one and only garden structure that comprises the twin round island of square pond(方池雙圓島) among the existing Jidangs in Korea. In this special Jidang, there are two coexisting islands that represent a well thought out garden facility for symbolizing conjugal affection and unyielding fidelity between master and servent(主從). In addition, the three inflows and one outflow facing the Ramcheon valley is regarded as an ideal garden design optimized for performing the function of a village bangjuk which is the site for undercurrent creation and ecological reprocessing. At present, Giant pussy willow is the only circular vegetation identified in the area of Bangcho pavilion, although this plant species is about to wither away judging from the signs of decrepitude that seems to persist for two out of three weeks. The old pine tree that appears in the 1872 Jeiyoung poetry of Byeongseon Song(宋秉璿) no longer exists. Anjae(安齋) Jang Yoo(張瑠)'s "Eight Scenary on Bangcho pavilion(芳草亭八詠)" and its expansive reproduction "Ten Scenary on Bangcho pavilion(芳草亭十景)" from Gwagang(守岡) Lee Manyoung(李晩永) depict vividly the pastoric scenery of an idyll(田園景) that stretches throughout the natural and cultural landscape of the province of Gimcheon and Guseong surrounding the Bangcho pavilion. The Bangcho pavilion sutra aims to establish Bangcho pavilion and the village of Wonteomaeul as the centre of microcosmos by dividing and allocating its scenic features according to the four seasons and times(四季四時), the eight courses(八方) and the meteorological phenomena, and it is the incarnation(顯現) of landscape perception upon the Byeol-seo Scenic site of Bangcho pavilion, the cultural hub of the region.

• Journal of Life Science
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• v.29 no.11
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• pp.1179-1191
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• 2019

Cancer cells undergo the epithelial-mesenchymal transition (EMT) and show unique oncogenic metabolic phenotypes such as the glycolytic switch (Warburg effect) which are important for tumor development and progression. The EMT is a critical process for tumor invasion and metastasis. High-mobility group box 1 (HMGB1) is a chromatin-associated nuclear protein, but it acts as a damage-associated molecular pattern molecule when released from dying cells and immune cells. HMGB1 induces the EMT, as well as invasion and metastasis, thereby contributing to tumor progression. Here, we show that HMGB1 induced the EMT by activating Snail. In addition, the HMGB1/Snail cascade was found induce a glycolytic switch. HMGB1 also suppressed mitochondrial respiration and cytochrome c oxidase (COX) activity by a Snail-dependent reduction in the expression of the COX subunits COXVIIa and COXVIIc. HMGB1 also upregulated the expression of several key glycolytic enzymes, including hexokinase 2 (HK2), phosphofructokinase-2/fructose-2,6-bisphosphatase 2 (PFKFB2), and phosphoglycerate mutase 1 (PGAM1), in a Snail-dependent manner. However, HMGB1 was found to regulate some other glycolytic enzymes including lactate dehydrogenases A and B (LDHA and LDHB), glucose transporter 1 (GLUT1), and monocarboxylate transporters 1 and 4 (MCT1 and 4) in a Snail-independent manner. Transfection with short hairpin RNAs against HK2, PFKFB2, and PGAM1 prevented the HMGB1-induced EMT, indicating that glycolysis is associated with HMGB1-induced EMT. These findings demonstrate that HMGB1 signaling induces the EMT, glycolytic switch, and mitochondrial repression via Snail activation.