• BMB Reports
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• v.41 no.3
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• pp.242-247
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• 2008

MSS, a comprising mixture of maesil (Prunus mume Sieb. et Zucc) concentrate, disodium succinate and Span80 (3.6 : 4.6 : 1 ratio) showed a significant improvement of memory when daily administered (460 mg/kg day, p.o.) into the normal rats for 3 weeks. During the spatial learning of 4 days in Morris water maze test, both working memory and short-term working memory index were significantly increased when compared to untreated controls. We investigated a molecular signal transduction mechanism of MSS on the behaviors of spatial learning and memory. MSS treatment increased hippocampal mRNA levels of NR2B and TrkB without changes of NR1, NR2A, ERK1, ERK2 and CREB. However, the protein levels of pERK/ERK and pCREB/CREB were all significantly increased to $1.5{\pm}0.17$ times. These results suggest that the improving effect of spatial memory for MSS is linked to MAPK/ERK signaling pathway that ends up in the phosphorylation of CREB through TrkB and/or NR2B of NMDA receptor.

• BMB Reports
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• v.48 no.8
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• pp.473-478
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• 2015

The NEK6 (NIMA-related kinases 6) is reported to play po-tential roles in tumorigenesis. Although it is suggested to function in several cellular pathways, the underlying mechanism in tumorigenesis is still largely unknown. In the present study, we discovered interaction of NEK6 with Smad4, a key member of transforming growth factor beta (TGFβ) pathway. Over-expression of NEK6 in hepatocellular carcinoma (HCC) cell lines suppresses TGFβ-mediated transcription activity in a kinase activity-dependent manner. In addition, NEK6 suppresses the cell growth arrest induced by TGFβ. Mechanically, NEK6 blocks nuclear translocation of Smad4, which is essential for TGFβ function. Moreover, we identified that NEK6 could be regulated by TGFβ and hypoxia. Our study sheds new light on the roles of NEK6 in canonical TGFβ/Smad pathway and tum-origenesis. [BMB Reports 2015; 48(8): 473-478]

• BMB Reports
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• v.45 no.12
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• pp.748-753
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• 2012

A sequence of 10 amino acids at the C-terminus region of methylglyoxal synthase from Escherichia coli (EMGS) provides an arginine, which plays a crucial role in forming a salt bridge with a proximal aspartate residue in the neighboring subunit, consequently transferring the allosteric signal between subunits. In order to verify the role of arginine, the gene encoding MGS from a thermophile species, Thermus sp. GH5 (TMGS) lacking this arginine was cloned with an additional 30 bp sequence at the 3'-end and then expressed in form of a fusion TMGS with a 10 residual segment at the C-terminus ($TMGS^+$). The resulting recombinant enzyme showed a significant increase in cooperativity towards phosphate, reflected by a change in the Hill coefficient (nH) from 1.5 to 1.99. Experiments including site directed mutagenesis for Asp-10 in TMGS and $TMGS^+$, two dimentional structural survey, fluorescence and irreversible thermoinactivation were carried out to confirm this pathway.

• Korean Journal of Biological Psychiatry
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• v.5 no.2
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• pp.219-226
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• 1998

Cytosine arabinoside(AraC) inhibits DNA synthesis and ${\beta}$-DNA polymerase, an enzyme involved in DNA repair. This, a potent antimitotic agent, is clinically used as an anticancer drug with side effect of severe neurotoxicity. Earlier reports suggested that inhibition of neuronal survival by AraC in sympathetic neuron may be due to the inhibition of a 2'-deoxycytidine-dependent process that is independent of DNA synthesis or repair and AraC induced a signal that is triggers a cascade of new mRNA and protein synthesis, leading to apoptotic cell death in cultured cerebellar granule cells. The present study would suggest whether caspase family(ICE/CED-3-like protease) involved in AraC-induced apoptosis pathway of PC12 cells. It was observed that treatment of PC12 cells with AraC led to decrease of viability by MTT assay and morphology changes, which did not suggest that AraC induced apoptosis in PC12 cells. The mRNA of caspase-1/caspase-3 were expressed in PC12 cells constitutively, and AraC did not activate caspase family. These results suggest that caspase-1/caspase-3 may not be required for AraC-induced cell death pathway in PC12 cells.

• BMB Reports
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• v.42 no.2
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• pp.65-71
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• 2009

Autophagy, which is a process of self eating, has gained interest in the past decade due to its both beneficial and controversial roles in various biological phenomena. The discovery of autophagy genes (ATG) in yeast has led to focused research designed to elucidate the mechanism and regulation of this process. The role of autophagy in a variety of biological phenomena, including human disease, is still the subject of debate. However, recent findings suggest that autophagy is a highly regulated process with both beneficial and negative effects. Indeed, studies conducted using various model organisms have demonstrated that increased autophagy leads to an extended lifespan. Despite these findings, it is still unknown if all pathways leading to extended lifespan converge at the process of autophagy or not. Here, an overview of modern developments related to the process of autophagy, its regulation and the molecular machinery involved is presented. In addition, this review focuses on one of the beneficial aspects of autophagy, its role in lifespan regulation.

• BMB Reports
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• v.49 no.11
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• pp.623-628
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• 2016

GPR78 is an orphan G-protein coupled receptor (GPCR) that is predominantly expressed in human brain tissues. Currently, the function of GPR78 is unknown. This study revealed that GPR78 was expressed in lung cancer cells and functioned as a novel regulator of lung cancer cell migration and metastasis. We found that knockdown of GPR78 in lung cancer cells suppressed cell migration. Moreover, GPR78 modulated the formation of actin stress fibers in A549 cells, in a RhoA- and Rac1-dependent manner. At the molecular level, GPR78 regulated cell motility through the activation of $G{\alpha}q$-RhoA/Rac1 pathway. We further demonstrated that in vivo, the knockdown of GPR78 inhibited lung cancer cell metastasis. These findings suggest that GPR78 is a novel regulator for lung cancer metastasis and may serve as a potential drug target against metastatic human lung cancer.

• Journal of Korean Neurosurgical Society
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• v.61 no.3
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• pp.352-362
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• 2018

Gliomas are the most common pediatric tumors of the central nervous system. In this review, we discuss the clinical features, treatment paradigms, and evolving concepts related to two types of pediatric gliomas affecting two main locations: the optic pathway and thalamus. In particular, we discuss recently revised pathologic classification, which adopting molecular parameter. We believe that our review contribute to the readers' better understanding of pediatric glioma because pediatric glioma differs in many ways from adult glioma according to the newest advances in molecular characterization of this tumor. A better understanding of current and evolving issues in pediatric glioma is needed to ensure effective management decision.

• Journal of Integrative Natural Science
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• v.8 no.4
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• pp.267-272
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• 2015

Galactosemia is a potentially lethal disorder caused by the deficiency of the enzyme galactose-1-phosphate uridyltransferase (GALT) within the Leloir pathway. Galactokinase (GALK) is the enzyme in Leloir pathway which converts ${\alpha}$-D galactose to galactose 1-phosphate. The elevated level of galactose-1-phosphate, the product of GALK plays a major role in Galactosemia. Therefore the inhibition of GALK is a novel therapy for this disorder. Hence in the present study, we performed molecular docking of twenty inhibitors with different activity against galactokinase into the active site of galactokinase enzyme. The binding mode of these inhibitors was obtained using Surflex dock program interfaced in Sybyl-X2.0. The residues such as SER141, TYR109, ARG105, ARG228, TYR106, GLY346, GLY136, ASP86, ASP186 and SER142 found to interact with inhibitors.

• BMB Reports
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• v.44 no.7
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• pp.423-434
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• 2011

A female hormone, estrogen, is linked to breast cancer incidence. Estrogens undergo phase I and II metabolism by which they are biotransformed into genotoxic catechol estrogen metabolites and conjugate metabolites are produced for excretion or accumulation. The molecular mechanisms underlying estrogen-mediated mammary carcinogenesis remain unclear. Cell proliferation through activation of estrogen receptor (ER) by its agonist ligands and is clearly considered as one of carcinogenic mechanisms. Recent studies have proposed that reactive oxygen species generated from estrogen or estrogen metabolites are attributed to genotoxic effects and signal transduction through influencing redox sensitive transcription factors resulting in cell transformation, cell cycle, migration, and invasion of the breast cancer. Conjuguation metabolic pathway is thought to protect cells from genotoxic and cytotoxic effects by catechol estrogen metabolites. However, methoxylated catechol estrogens have been shown to induce ER-mediated signaling pathways, implying that conjugation is not a simply detoxification pathway. Dual action of catechol estrogen metabolites in mammary carcinogenesis as the ER-signaling molecules and chemical carcinogen will be discussed in this review.

• Toxicological Research
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• v.15 no.1
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• pp.89-93
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• 1999

2,3,7,8-Tetrachlorodibenzo-p-dioxin(TCDD) is known to induce cytochrome p450 1A1 and to activate c-Src kinase and p21 Ras. This study examined the molecular interactions of adaptor proteins including Shc, Grb2, and Sos in rat primary hepatocytes and their relationship to the induction of CYP1A1 by TCDD. TCDD induced CYP1A1 level and EROD activity in a dose-dependent mode. Sos/Grb2 association isincreased by TCDDㅑㅜ a dose dependent mode. Tyrosine phosphorylated Shc, mainly p152, onloads to Grb2/Sos complex upon TCDD stimulation. The electrophoretic mobility shift of Sos is showed by TCDD. These results indicate that TCDD modulated the molecular interaction features of adaptor compoes proteins including Shc, Grb2, and Cnl in early signaling pathway of TCDD-mediated CYP 1A1 induction of rat primary hepatocyte.