• BMB Reports
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• v.45 no.11
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• pp.653-658
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• 2012

After the outbreak of the swine-origin influenza A H1N1 virus in April 2009, World Health Organization declared this novel H1N1 virus as the first pandemic influenza virus (2009 pH1N1) of the $21^{st}$ century. To elucidate the characteristics of 2009 pH1N1, the growth properties of A/Korea/01/09 (K/09) was analyzed in cells. Interestingly, the maximal titer of K/09 was higher than that of a seasonal H1N1 virus isolated in Korea 2008 (S/08) though the RNP complex of K/09 was less competent than that of S/08. In addition, the NS1 protein of K/09 was determined as a weak interferon antagonist as compared to that of S/08. Thus, in order to confine genetic determinants of K/09, activities of two major surface glycoproteins were analyzed. Interestingly, K/09 possesses highly reactive NA proteins and weak HA cell-binding avidity. These findings suggest that the surface glycoproteins might be a key factor in the features of 2009 pH1N1.

• BMB Reports
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• v.48 no.11
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• pp.597-598
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• 2015

Mitochondrial respiratory defect is a key bioenergetics feature of hepatocellular carcinoma (HCC) cells. However, their involvement and roles in HCC development and progression remain unclear. Recently, we identified 10 common mitochondrial defect (CMD) signature genes that may be induced by retrograde signaling-mediated transcriptional reprogramming in response to HCC mitochondrial defects. HCC patients with enriched expression of these genes had poor prognostic outcomes, such as shorter periods of overall survival and recurrence-free survival. Nuclear protein 1 (NUPR1), a key transcription regulator, was up-regulated by Ca⁺⁺-mediated retrograde signaling. NUPR1-centric network analysis and a biochemical promoter-binding assay demonstrated that granulin (GRN) is a key downstream effector of NUPR1 for the regulation of HCC cell invasiveness; association analysis of the NUPR1-GRN pathway supported this conclusion. Mitochondrial respiratory defects and retrograde signaling thus play pivotal roles in HCC progression, highlighting the potential of the NUPR1-GRN axis as a novel diagnostic marker and therapeutic target for HCC.

• Bulletin of the Korean Chemical Society
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• v.35 no.7
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• pp.2097-2108
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• 2014

Chemical feature based quantitative pharmacophore models were generated using the HypoGen module implemented in DS2.5. The best hypothesis, Hypo1, which was characterized by the highest correlation coefficient (0.96), the highest cost difference (61.60) and the lowest RMSD (0.74), consisted of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic and one ring aromatic. The reliability of Hypo1 was validated on the basis of cost analysis, test set, Fischer's randomization method and GH test method. The validated Hypo1 was used as a 3D search query to identify novel inhibitors. The screened molecules were further refined by employing ADMET, docking studies and visual inspection. Three compounds with novel scaffolds were selected as the most promising candidates for the designing of Mcl-1 antagonists. Finally, a 10 ns molecular dynamics simulation was carried out on the complex of receptor and the retrieved ligand to demonstrate that the binding mode was stable during the MD simulation.

• Journal of Yeungnam Medical Science
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• v.30 no.1
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• pp.4-9
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• 2013

Leptin, a 16-kDa cytokine, is secreted by adipose tissue in response to the surplus of fat store. Thereby, the brain is informed about the body's energy status. In the hypothalamus, leptin triggers specific neuronal subpopulations (e.g., POMC and NPY neurons) and activates several intracellular signaling events, including the JAK/STAT, MAPK, PI3K, and mTOR pathway, which eventually translates into decreased food intake and increased energy expenditure. Leptin signal is inhibited by a feedback inhibitory pathway mediated by SOCS3. PTP1B involves another inhibitory pathway of leptin. Leptin potently promotes fat mass loss and body weight reduction in lean subjects. However, it is not widely used in the clinical field because of leptin resistance, which is a common feature of obesity characterized by hyperleptinemia and the failure of exogenous leptin administration to provide therapeutic benefit in rodents and humans. The potential mechanisms of leptin resistance include the following: 1) increases in circulating leptin-binding proteins, 2) reduced transport of leptin across the blood-brain barrier, 3) decreased leptin receptor-B (LRB), and/or 4) the provocation of processes that diminish cellular leptin signaling (inflammation, endoplasmic reticulum stress, feedback inhibition, etc.). Thus, interference of the cellular mechanisms that attenuate leptin signaling improves leptin action in cells and animal models, suggesting the potential utility of these processes as points of therapeutic intervention. Various experimental trials and compounds that improve leptin resistance are introduced in this paper.

• YAKHAK HOEJI
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• v.52 no.2
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• pp.111-116
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• 2008

Diethylstilbestrol (DESB) is a synthetic estrogen not only that routinely prescribed, but also that known to be a teratogen. In this study, we found a novel pharmacological feature that DESB is able to positively modulate CD29 $({\beta}1-integrin)$ function. Thus, DESB up-regulated homotypic cell-cell adhesion of monocytic U937 cells mediated by CD29. However, DESB did not increase the surface level of CD29 and its binding activity to ligand (fibronectin), according to flow cytometric analysis and cell-fibronectin adhesion assay. Instead, the DESB-mediated up-regulation of cell-cell adhesion was blocked by several signaling enzyme inhibitors. Treatment of U0126 [an extracellular signal-regulated kinase (ERK) inhibitor], SB20358 (a p38 inhibitor) or Rp-8-pCPT-cGMP (a protein kinase G inhibitor) clearly inhibited DESB-mediated up-regulation of cell-cell adhesion induced by CD29. However, estrogen receptor antagonist ICI 182,780 failed to abrogate DESB effect. Therefore, our data suggest that DESB may up-regulate CD29-mediated cell-cell adhesion via modulating intracellular signaling enzymes such as ERK, PKG, and p38, independent of estrogen receptor function.

• BMB Reports
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• v.51 no.1
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• pp.5-13
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• 2018

Formation of toxic protein aggregates is a common feature and mainly contributes to the pathogenesis of neurodegenerative diseases (NDDs), which include amyotrophic lateral sclerosis (ALS), Alzheimer's, Parkinson's, Huntington's, and prion diseases. The transglutaminase 2 (TG2) gene encodes a multifunctional enzyme, displaying four types of activity, such as transamidation, GTPase, protein disulfide isomerase, and protein kinase activities. Many studies demonstrated that the calcium-dependent transamidation activity of TG2 affects the formation of insoluble and toxic amyloid aggregates that mainly consisted of NDD-related proteins. So far, many important and NDD-related substrates of TG2 have been identified, including $amlyoid-{\beta}$, tau, ${\alpha}-synuclein$, mutant huntingtin, and ALS-linked trans-activation response (TAR) DNA-binding protein 43. Recently, the formation of toxic inclusions mediated by several TG2 substrates were efficiently inhibited by TG2 inhibitors. Therefore, the development of highly specific TG2 inhibitors would be an important tool in alleviating the progression of TG2-related brain disorders. In this review, the authors discuss recent advances in TG2 biochemistry, several mechanisms of molecular regulation and pleotropic signaling functions, and the presumed role of TG2 in the progression of many NDDs.

• Journal of Biomedical Engineering Research
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• v.27 no.4
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• pp.170-179
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• 2006

The purpose of this study was to investigate the spatiotemporal cortical activation pattern and functional connectivity during visual perception of words. 61 channel recordings of electroencephalogram were obtained from 15 subjects while they were judging the meaning of Korean, English, and Chinese words with concrete meanings. We examined event-related potentials (ERP) and applied independent component analysis (ICA) to find and separate simultaneously activated neural sources. Spectral analysis was also performed to investigate the gamma-band activity (GBA, 30-50 Hz) which is known to reflect feature binding. Five significant ERP components were identified and left hemispheric dominance was observed for most sites. Meaningful differences of amplitudes and latencies among languages were observed. It seemed that familiarity with each language and orthographic characteristics affected the characteristics of ERP components. ICA helped confirm several prominent sources corresponding to some ERP components. The results of spectral and time-frequency analyses showed distinct GBAs at prefrontal, frontal, and temporal sites. The GBAs at prefrontal and temporal sites were significantly correlated with the LPC amplitude and response time. The differences in spatiotemporal patterns of GBA among languages were not prominent compared to the inter-individual differences. The gamma-band coherence revealed short-range connectivity within frontal region and long-range connectivity between frontal, posterior, and temporal sites.

• Korean Journal of Microbiology
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• v.43 no.4
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• pp.250-255
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• 2007

The RecA protein of Deinococcus radiodurans is essential for the extreme radiation resistance of this organism. The central steps involved in recombinational DNA repair require DNA-dependent ATP hydrolysis by recA protein. Key feature of RecA protein-mediated activities is the interactions with ssDNA and dsDNA. The ssDNA is the site where RecA protein filament formation nucleates and where initiation of DNA strand exchange takes place. The effect of sequence heterogeneity of ssDNA was examined in this experiment. The rate of homopolymeric synthetic ssDNA-dependent ATP hydrolysis was constant or nearly so over a broader range of pHs. For poly(dT)-dependent ATP or dATP hydrolysis, rates were generally faster, with a broader optimum between pH 7.0 and 8.0. Activities of RecA protein were affected by the ionic environment. The ATPase activity was shown to have different sensitivity to anionic species. The presence of glutamate seemed to slimulate the hydrolytic activity. Dr RecA protein was shown to require $Mg^{2+}$ ion greater than 2 mM for binding to etheno ssDNA and the binding stoichiometry of 3 nucleotide for RecA protein monomer.

• Anatomy and Cell Biology
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• v.51 no.4
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• pp.274-283
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• 2018

Hyper-O-GlcNAcylation is a general feature of cancer which contributes to various cancer phenotypes, including cell proliferation and cell growth. Quercetin, a naturally occurring dietary flavonoid, has been reported to reduce the proliferation and growth of cancer. Several reports of the anticancer effect of quercetin have been published, but there is no study regarding its effect on O-GlcNAcylation. The aim of this study was to investigate the anticancer effect of quercetin on HeLa cells and compare this with its effect on HaCaT cells. Cell viability and cell death were determined by MTT and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling assays. O-GlcNAcylation of AMP-activated protein kinase (AMPK) was examined by succinylated wheat germ agglutinin pulldown and immunoprecipitation. Immunofluorescence staining was used to detect the immunoreactivitiy of O-linked N-acetylglucosamine transferase (OGT) and sterol regulatory element binding protein 1 (SREBP-1). Quercetin decreased cell proliferation and induced cell death, but its effect on HaCaT cells was lower than that on HeLa cells. O-GlcNAcylation level was higher in HeLa cells than in HaCaT cells. Quercetin decreased the expression of global O-GlcNAcylation and increased AMPK activation by reducing the O-GlcNAcylation of AMPK. AMPK activation due to reduced O-GlcNAcylation of AMPK was confirmed by treatment with 6-diazo-5-oxo-L-norleucine. Our results also demonstrated that quercetin regulated SREBP-1 and its transcriptional targets. Furthermore, immunofluorescence staining showed that quercetin treatment decreased the immunoreactivities of OGT and SREBP-1 in HeLa cells. Our findings demonstrate that quercetin exhibited its anticancer effect by decreasing the O-GlcNAcylation of AMPK. Further studies are needed to explore how quercetin regulates O-GlcNAcylation in cancer.

• Molecules and Cells
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• v.24 no.3
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• pp.416-423
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• 2007

Alterations in the glycan chains of cell surface glycoconjugates are frequently involved biological processes such as cell-cell interaction, cell migration, differentiation and development. Cultured embryonic (E18) rat cortical neurons underwent apoptosis in response to camptothecin, and lectin histochemistry showed that binding to apoptotic neurons of FITC-conjugated Maackia amurensis agglutinin (MAA), which is specific for terminal ${\alpha}2,3$-sialic acid residues, increased progressively with increasing concentrations of camptothecin. Analysis of the total proteins of apoptotic neurons by SDS-PAGE, and lectin blotting using HRP-labeled MAA, revealed that the expression of terminal ${\alpha}2,3$-sialic acid residues on an unknown protein with an apparent molecular mass of 25.6 kDa also increased in apoptotic neurons. NP-HPLC analysis of the total cellular N-glycans of normal and apoptotic neurons demonstrated that the expression of structurally simpler biantennary types of N-glycans fell by 49% during apoptosis whereas the more branched triantennary types of N-glycans with terminal sialic acid residues increased by up to 59%. These results suggest that increased surface expression of ${\alpha}2,3$-sialic acid residues and hyperglycosylation of N-glycans is a common feature of cellular responses to changes in cell physiology such as tumorigenesis and apoptosis.