• Toxicological Research
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• v.24 no.1
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• pp.1-9
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• 2008

Ptdlns(4,5)$P_2$ is a key cellular phosphoinositide that localizes in separate and distinctive pools in subcellular membrane and vesicular compartments. In membranes, Ptdlns(4,5)$P_2$ acts as a precursor to second messengers and is itself a main signaling and targeting molecule. Specific subcellular localization of type I PIP kinases directed by interacting with specific targeting module differentiates Ptdlns(4,5)$P_2$ production in a spatial and temporal manner. Several lines of evidences support the idea that Ptdlns(4,5)$P_2$ is generated in very specific pools in a spatial and temporal manner or by feeding Ptdlns(4,5)$P_2$ directly to effectors. In this concept, the interaction of PIPKI isoforms with a specific targeting module to allow precise subcellular targeting modulates highly specific Ptdlns(4,5)$P_2$ synthesis and channeling overall effectors. For instance, localization of PIPKI${\gamma}$661 to focal adhesions by an interaction with talin results in spatial and temporal production of Ptdlns(4,5)$P_2$, which regulates EGF-stimulated directional cell migration. In addition, Type $I{\gamma}$ PIPK is targeted to E-cadherin in cell adherence junction and plays a role in controlling dynamics of cell adherence junction and endocytosis of E-cadherin. Characterizing how PIP kinase isoforms are regulated by interactions with their targeting modules, as well as the mechanisms by which their product, Ptdlns(4,5)$P_2$, exerts its effects on cellular signaling processes, is crucial to understand the harmonized control of numerous cellular signaling pathways. Thus, in this review the roles of the Ptdlns(4)P(5) kinases and Ptdlns(4,5)$P_2$ were described and critically reviewed in terms of regulation of the E-cadherin trafficking, cell migration, and formation of cell adherence junction which is indispensable and is tightly controlled in epithelial-to-mesenchymal transition process.

• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.122-128
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• 2014

The stiffness of cancer cells is attributable to intermediate filaments such as keratin. Perinuclear reorganization via phosphorylation of specific serine residue in keratin is implicated in the deformability of metastatic cancer cells including the human pancreatic carcinoma cell line (PANC-1). 12-O-Tetradecanoylphorbol-13-acetate (TPA) is a potent tumor promoter and protein kinase C (PKC) activator. However, its effects on phosphorylation and reorganization of keratin 8 (K8) are not well known. Therefore, we examined the underlying mechanism and effect of TPA on K8 phosphorylation and reorganization. TPA induced phosphorylation and reorganization of K8 and transglutaminase-2 (Tgase-2) expression in a time- and dose-dependent manner in PANC-1 cells. These effects peaked after 45 min and 100 nM of TPA treatment. We next investigated, using cystamine (CTM), Tgase inhibitor, and Tgase-2 gene silencing, Tgase-2's possible involvement in TPA-induced K8 phosphorylation and reorganization. We found that Tgase-2 gene silencing inhibited K8 phosphorylation and reorganization in PANC-1 cells. Tgase-2 gene silencing, we additionally discovered, suppressed TPA-induced migration of PANC-1 cells and Tgase-2 overexpression induced migration of PANC-1 cells. Overall, these results suggested that TPA induced K8 phosphorylation and reorganization via Tgase-2 expression in PANC-1 cells.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.40 no.6
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• pp.367-373
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• 2007

We assessed the stock of the southern bluefin tuna (SBT, Thunnus maccoyii) by applying the MULTIFAN-CL model. The model is spatially disaggregated, with the population and fisheries stratified into a number of regions within the overall stock range. Catch, effort, length-frequency, and tagging data from 1965 to 2003 were stratified by three regions and four quarters (Jan-Mar, Apr-Jun, Jul-Sept and Oct-Dec). These data were used to estimate the instantaneous fishing mortality (F), biomass, spawning biomass, recruitment, and so on. The Commission for the Conservation of Southern Bluefin Tuna (CCSBT) used only Japanese data and did not consider migration for the SBT stock assessment. By contrast, we used Japanese, Australian, New Zealand, Taiwanese, and Korean data, and considered migration. As a result, the estimated annual average F of all age classes was 0.073/yr and the F of age class 6-10 was the highest. The results also showed that the biomass and recruitment of SBT had declined significantly after 1965. Compared with the CCSBT results, the estimated spawning biomass in this study was lower and more uncertain. However, we will conduct a sensitivity analysis to get more accurate biological parameters and results. In addition, we need to use the bootstrap resampling method to quantify the uncertainty.

• Fisheries and Aquatic Sciences
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• v.21 no.6
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• pp.16.1-16.7
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• 2018

Background: Matrix metalloproteinases (MMPs) are linked with several complications such as metastasis of cancer progression, oxidative stress, and hepatic fibrosis. Brown seaweeds are being extensively studied for their bioactive molecule content against cancer progression. In this context, Sargassum horneri was reported to possess various bioactivities including antiviral, antimicrobial, and anti-inflammatory partly due to its phenolic compound content. Methods: In this study, potential of S. horneri was evaluated through anti-MMP effect in HT1080 fibrosarcoma cells. S. horneri crude extract was fractionated with organic solvents, namely, water ($H_2O$), n-buthanol (n-BuOH), 85% aqueous methanol (85% aq. MeOH), and n-hexane. The non-toxicity of fraction samples (Sargassum horneri solvent-partitioned extracts (SHEs)) was confirmed by cell-viability assay. SHEs were tested for their ability to inhibit MMP enzymatic activity through gelatin digestion evaluation and cell migration assay. Expressions of MMP-2 and MMP-9 and tissue inhibitors of MMP (TIMPs) were evaluated by reverse transcription and Western blotting. Results: All fractions inhibited the enzymatic activities of MMP-2 and MMP-9 according to gelatin zymography. Except $H_2O$ fraction, fractions hindered the cell migration significantly. All tested fractions suppressed both mRNA and protein levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. Conclusion: Overall, current results suggested that S. horneri has potential to be a good source for anti-MMP agents, and further investigations are underway for better understanding of the action mechanism and isolation and elucidation of the bioactive molecules.

• Molecules and Cells
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• v.43 no.6
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• pp.551-571
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• 2020

Nuclear receptor-related 1 (Nurr1) protein has been identified as an obligatory transcription factor in midbrain dopaminergic neurogenesis, but the global set of human NURR1 target genes remains unexplored. Here, we identified direct gene targets of NURR1 by analyzing genome-wide differential expression of NURR1 together with NURR1 consensus sites in three human neural stem cell (hNSC) lines. Microarray data were validated by quantitative PCR in hNSCs and mouse embryonic brains and through comparison to published human data, including genome-wide association study hits and the BioGPS gene expression atlas. Our analysis identified ~40 NURR1 direct target genes, many of them involved in essential protein modules such as synapse formation, neuronal cell migration during brain development, and cell cycle progression and DNA replication. Specifically, expression of genes related to synapse formation and neuronal cell migration correlated tightly with NURR1 expression, whereas cell cycle progression correlated negatively with it, precisely recapitulating midbrain dopaminergic development. Overall, this systematic examination of NURR1-controlled regulatory networks provides important insights into this protein's biological functions in dopamine-based neurogenesis.

• Journal of the Korea Fashion and Costume Design Association
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• v.23 no.3
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• pp.23-42
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• 2021

The purpose of this study is to analyze the characteristics of the Chinese Miao people's Batik patterns and provide data in the field of fashion design for the utilization of the traditional patterns. This study investigated and analyzed the regional characteristics of Batik dyeing, which was listed on China's national intangible cultural heritage list; Danzhai, Anshun, Huangping, and Gonghyeon. The expressive characteristics were classified into four categories: symbolism, abstraction, decorativeness, and playfulness. The results are as follows. First, symbolism can be classified into the origins of the Miao, symbols of faith, history of migration, and the symbols of status with Batik patterns from different regions, seemingly involving various symbolic implications. Due to the absence of letters, Miao people expressed their emotions and history in the design patterns. A series of developments in recent years has led to incorporating the temperament of the Miao people, history of migration, expression of emotions, and ideal hopes in Batik dyed design patterns and the symbolic functions have been significantly emphasized. Second, the decorativeness is mainly characterized by repeated patterns of the Miao Batik dyeing design. The overall patterns demonstrate design features characterized by regularization and simplification, along with a sense of rhythm with the unique arrangement of patterns. Third, the abstractness of the Batik dyeing design patterns is often found in plant and animal patterns, properly delivering new designs created by Miao women by extracting and rearranging various elements, including dots, lines, and faces shown in natural images. Fourth, playfulness is expressed by the transformation and distortion of Miao Batik patterns, and were created by applying patterns or other elements to original forms to express animal or plant patterns in a playful way.

• Journal of Korean Neurosurgical Society
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• v.64 no.1
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• pp.60-68
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• 2021

Objective : Until recently, the transfemoral approach (TFA) was used as the primary method of arterial approach in acute ischemic stroke (AIS). However, TFA resulted in longer reperfusion times and worse outcomes in the mechanical thrombectomy (MT) of patients with complex aortic arches and significant carotid tortuosity. We found that the transradial approach (TRA) is a more favorable alternative approach for MT in such cases. Methods : We performed a retrospective review of our institutional database to identify 202 patients who underwent MT for AIS between February 2015 and December 2019. Patient characteristics, cause of TFA failure, procedure time, intra-procedural complications, and outcomes were recorded. Results : Eleven (5.4%) of 202 patients, who underwent MT for AIS, crossed over to TRA for recanalization, and eight (72%) of 11 achieved successful recanalization (≥modified Treatment in Cerebral Infarction 2b). The mean age (mean±standard deviation [median]) was 82.3±6.6 (76) years, and five of the 11 patients were male. The last seen normal to puncture time was 467.9±264.72 (264) minutes; baseline National Institutes of Health Stroke Scale score was 28.9±14.5 (16). Six (55%) of the 11 patients had right vertebrobasilar occlusions, and the remaining five (45%) had anterior circulation occlusive disease. The time from groin puncture to final recanalization time (overall procedural time) was 78.0±20.1 (62) minutes. The mean crossover time from TFA to TRA was 45.2±10.5 (41) minutes. The mean time from radial puncture to final recanalization was 33.8±10.5 (28) minutes. Distal thrombus migration events in previously unaffected territories occurred in 3/8 patients (37%). At 90 days, three patients (28%) had a favorable clinical outcome. Conclusion : Although rare, failure of TFA has been known to occur during MT for AIS. Our results demonstrate that TRA may be an alternative option for AIS intervention for select patients with subsequent timely revascularization. However, the incidence of distal thrombus migration was high, and the first puncture to reperfusion time was prolonged because of the time taken for the crossover to TRA after failure of TFA. This study provides some evidence that the TRA may be a viable alternative option to the TFA for MT of AIS.

• Molecules and Cells
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• v.45 no.4
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• pp.202-215
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• 2022

The androgen receptor (AR) is an important therapeutic target for treating prostate cancer (PCa). Moreover, there is an increasing need for understanding the AR-independent progression of tumor cells such as neuroendocrine prostate cancer (NEPC). Menin, which is encoded by multiple endocrine neoplasia type 1 (MEN1), serves as a direct link between AR and the mixed-lineage leukemia (MLL) complex in PCa development by activating AR target genes through histone H3 lysine 4 methylation. Although menin is a critical component of AR signaling, its tumorigenic role in AR-independent PCa cells remains unknown. Here, we compared the role of menin in AR-positive and AR-negative PCa cells via RNAi-mediated or pharmacological inhibition of menin. We demonstrated that menin was involved in tumor cell growth and metastasis in PCa cells with low or deficient levels of AR. The inhibition of menin significantly diminished the growth of PCa cells and induced apoptosis, regardless of the presence of AR. Additionally, transcriptome analysis showed that the expression of many metastasis-associated genes was perturbed by menin inhibition in AR-negative DU145 cells. Furthermore, wound-healing assay results showed that menin promoted cell migration in AR-independent cellular contexts. Overall, these findings suggest a critical function of menin in tumorigenesis and provide a rationale for drug development against menin toward targeting high-risk metastatic PCa, especially those independent of AR.

• Development and Reproduction
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• v.25 no.2
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• pp.93-104
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• 2021

Cutaneous melanoma is a fatal disease for patients with distant metastasis. Metformin is the most widely used anti-diabetic drug, and proved to suppress cell proliferation and metastasis in diverse cancers including melanoma. We previously reported that MEK inhibitor trametinib increases the expression of epithelial-mesenchymal transition (EMT) regulators and melanoma cell motility, which are suppressed by addition of metformin in A375 melanoma cells. To confirm our findings further, we first evaluated the effect of metformin in combination with another MEK inhibitor binimetinib on cell viability in G361 melanoma cells. We then investigated whether binimetinib affects the expression of EMT regulators and cell motility. We finally monitored the effect of metformin on binimetinib-induced cell migration. Cell viability assay showed that combination index (CI) value at ED₅₀ is 0.80, suggesting synergy for the combination of metformin with binimetinib. Our results also revealed that binimetinib increased the expression of EMT regulators such as integrin αV, fibronectin and slug, which correlate well with the enhanced cell migration in wound healing assay. Metformin, on the contrary, suppressed the expression of sparc, integrin αV, fibronectin and N-cadherin with the reduced cell motility. The combination treatment showed that metformin counteracts the binimetinib-induced increase of cell motility. Overall, these results suggest that metformin with binimetinib might be useful as a potential therapeutic adjuvant against cell survival and metastatic activity in melanoma patients.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.3
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• pp.183-193
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• 2022

MicroRNAs (miRNAs) regulate gene expression and are biomarkers for coronary atherosclerosis (AS). A novel miRNA-mRNA regulation network of coronary AS still needs to be disclosed. The aim of this study was to analyze potential mRNAs in coronary AS patients and the role of their upstream miR-491-5p in vascular smooth muscle cells (VSMCs). We first confirmed top ten mRNAs according to the analysis from Gene Expression Omnibus database (GSE132651) and examined the expression levels of them in the plaques and serum from AS patients. Five mRNAs (UBE2G2, SLC16A3, POLR2C, PNO1, and AMDHD2) presented significantly abnormal expression in both plaques and serum from AS patients, compared with that in the control groups. Subsequently, they were predicted to be targeted by 11 miRNAs by bioinformatics analysis. Among all the potential upstream miRNAs, only miR-491-5p was abnormally expressed in the plaques and serum from AS patients. Notably, miR-491-5p overexpression inhibited viability and migration, and significantly increased the expression of contractile markers (α-SMA, calponin, SM22α, and smoothelin) in VSMCs. While silencing miR-491-5p promoted viability and migration, and significantly suppressed the expression of α-SMA, calponin, SM22α, and smoothelin. Overall, miR-491-5p targeted UBE2G2, SLC16A3, and PNO1 and regulated the dysfunctions in VSMCs.