• BMB Reports
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• 제31권5호
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• pp.468-474
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• 1998

Membrane depolarization in PC12 cells induces calcium influx via an L-type voltage-sensitive calcium channel (L-VSCC) and increases intracellular free calcium, which leads to tyrosine phosphorylation of epidermal growth factor (EGF) receptor and the associated adaptor protein, She. This activated EGF receptor complex then can activate mitogen-activated protein (MAP) kinase, as in nerve growth factor (NGF) receptor activation. In the present study, we investigated the role of EGF receptor in the signaling pathway initiated by membrane depolarization of PC12 cells. Prolonged membrane depolarization induced phosphorylation of extracellular signal-regulated kinase (ERK) within 1 min in undifferentiated PC12 cells. Pretreatment of PC12 cells with the calcium chelator EGTA abolished depolarization-stimulated ERK phosphorylation, but NGF-induced phosphorylation of ERK was not affected. The chronic treatment of phorbol ester, which down-regulated the activity of protein kinase C (PKC), did not affect the phosphorylation of ERK upon depolarization. In the presence of an inhibitor of EGF receptor, neither depolarization nor calcium ionophore increased the level of ERK phosphorylation. These data imply that the EGF receptor is functionally necessary to activate ERK and neurite outgrowth in response to the prolonged depolarization in PC12 cells, and also that PKC is apparently not involved in this signaling pathway.

• The Plant Pathology Journal
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• 제35권6호
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• pp.684-691
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• 2019

Evolution of adaptive mechanisms to abiotic stress is essential for plant growth and development. Plants adapt to stress conditions by activating the abscisic acid (ABA) signaling pathway. It has been suggested that the ABA receptor, clade A protein phosphatase, SnRK2 type kinase, and SLAC1 anion channel are important components of the ABA signaling pathway. In this study, we report that the shaker type potassium (K⁺) channel, GORK, modulates plant responses to ABA and abiotic stresses. Our results indicate that the full length of PP2CA is needed to interact with the GORK C-terminal region. We identified a loss of function allele in gork that displayed ABA-hyposensitive phenotype. gork and pp2ca mutants showed opposite responses to ABA in seed germination and seedling growth. Additionally, gork mutant was tolerant to the NaCl and mannitol treatments, whereas pp2ca mutant was sensitive to the NaCl and mannitol treatments. Thus, our results indicate that GORK enhances the sensitivity to ABA and negatively regulates the mechanisms involved in high salinity and osmotic stresses via PP2CA-mediated signals.

• 생약학회지
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• 제45권2호
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• pp.127-134
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• 2014

A great interest is emerging about green tea as a tool against human cancer proliferation or inflammation, as pointed out by recent reports describing the inhibitory action of epigallocatechin gallate (EGCG) on angiogenesis, urokinase, metalloproteinases, and induction of inducible nitric oxide synthase. We proposed that EGCG may regulate a multi target signaling having wider spectra of action than those actions of single enzymes. CSK (c-terminal Src kinase) protein is a non-receptor tyrosine kinase involved in the cross-talk and mediation of many signaling pathways that promote cell proliferation, adhesion, invasion, migration, and tumorigenesis. Based on the knowledge that CSK activation is important for cancer proliferation we hypothesized that CSK could be a target of EGCG. Here we showed that EGCG effectively suppressed the growth of CSK MEF cell when compare with CSK knockout MEF cell growth. These results indicate that EGCG could be used as a chemoprevention to modulate CSK signal pathway in inflammatory processes and tumor formation.

• Molecules and Cells
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• 제19권3호
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• pp.342-349
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• 2005

Cytokinins are adenine derivatives that regulate numerous plant growth and developmental processes, including apical and floral meristem development, stem growth, leaf senescence, apical dominance, and stress tolerance. However, not much is known about how cytokinin biosynthesis and metabolism is regulated. We identified a novel Arabidopsis gene, ALL, encoding an aldolase-like enzyme that regulates cytokinin signaling. An Arabidopsis mutant, all-1D, in which ALL is activated by the nearby insertion of the 35S enhancer, exhibited extreme dwarfism with rolled, dark-green leaves and reduced apical dominance, symptomatic of cytokinin-overproducing mutants. Consistent with this, ARR4 and ARR5, two representative primary cytokinin-responsive genes, were significantly induced in all-1D. Whereas SHOOT MERISTEMLESS (STM) and KNAT1, which regulate meristem development, were also greatly induced, expression of REV and PHV that regulate lateral organ polarity was inhibited. ALL encodes an aldolase-like enzyme that belongs to the HpcH/HpaI aldolase family in prokaryotes and is down-regulated by exogenous cytokinin, possibly through a negative feedback pathway. We propose that ALL is involved in cytokinin biosynthesis or metabolism and acts as a positive regulator of cytokinin signaling during shoot apical meristem development and determination of lateral organ polarity.

• KSBB Journal
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• 제25권6호
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• pp.507-512
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• 2010

In this study, we investigated the ability of luteolin, a plant derived flavonoid on hepatocarcinoma cell growth using HepG2 cell culture system. We found that luteolin increased the Smac/DIABLO releases, a mitochondrial protein that potentiates apoptosis. Luteolin also induced either transcriptional activity or expression of PPAR-gamma, a target of cancer growth that PPAR-gamma agonist sensitizes to apoptosis in certain cancer types. To find the possible upstream target molecules of PPAR-gamma activated by luteolin treatment, we used compound C, a specific inhibitor of AMP-activated protein kinase. Pre-treatment of Compound C significantly restored the activation or expression of PPAR-gamma stimulated by luteolin. This result indicated that AMPK signaling might be involved in the activation or expression of PPAR-gamma signaling pathway stimulated by luteolin. Moreover, we also found that luteolin inhibited the insulin-stimulated Akt phosphorylation as well as AICAR, a specific AMPK activator. These results propose that luteolin significantly induces cancer cell death through modulating survival signal pathways such as PPAR-gamma and Akt. AMPK signaling pathway may be an upstream regulator for survival signal pathways such as PPAR-gamma and Akt stimulated by luteolin.

• Molecules and Cells
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• 제40권7호
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• pp.515-522
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• 2017

CD133, a pentaspan transmembrane glycoprotein, is generally used as a cancer stem cell marker in various human malignancies, but its biological function in cancer cells, especially in glioma cells, is largely unknown. Here, we demonstrated that forced expression of CD133 increases the expression of IL-$1{\beta}$ and its downstream chemokines, namely, CCL3, CXCL3 and CXCL5, in U87MG glioma cells. Although there were no apparent changes in cell growth and sphere formation in vitro and tumor growth in vivo, in vitro trans-well studies and in vivo tumor xenograft assays showed that neutrophil recruitment was markedly increased by the ectopic expression of CD133. In addition, the clinical relevance between CD133 expression and IL-$1{\beta}$ gene signature was established in patients with malignant gliomas. Thus, these results imply that glioma cells expressing CD133 are capable of modulating tumor microenvironment through the IL-$1{\beta}$ signaling pathway.

• Biomolecules & Therapeutics
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• 제25권3호
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• pp.321-328
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• 2017

Steroid sulfatase (STS) is an enzyme responsible for the hydrolysis of aryl and alkyl sulfates. STS plays a pivotal role in the regulation of estrogens and androgens that promote the growth of hormone-dependent tumors, such as those of breast or prostate cancer. However, the molecular function of STS in tumor growth is still not clear. To elucidate the role of STS in cancer cell proliferation, we investigated whether STS is able to regulate the integrin signaling pathway. We found that overexpression of STS in HeLa cells increases the protein and mRNA levels of integrin ${\beta}1$ and fibronectin, a ligand of integrin ${\alpha}5{\beta}1$. Dehydroepiandrosterone (DHEA), one of the main metabolites of STS, also increases mRNA and protein expression of integrin ${\beta}1$ and fibronectin. Further, STS expression and DHEA treatment enhanced phosphorylation of focal adhesion kinase (FAK) at the Tyr 925 residue. Moreover, increased phosphorylation of ERK at Thr 202 and Tyr 204 residues by STS indicates that STS activates the MAPK/ERK pathway. In conclusion, these results suggest that STS expression and DHEA treatment may enhance MAPK/ERK signaling through up-regulation of integrin ${\beta}1$ and activation of FAK.

• Journal of Microbiology and Biotechnology
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• 제32권1호
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• pp.126-140
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• 2022

Stem cells can be applied usefully in basic research and clinical field due to their differentiation and self-renewal capacity. The aim of this study was to establish an effective novel therapeutic cellular source and create its molecular expression profile map to elucidate the possible therapeutic mechanism and signaling pathway. We successfully obtained a mesenchymal stem cell population from human embryonic stem cells (hESCs) cultured on chemically defined feeder-free conditions and treated with connective tissue growth factor (CTGF) and performed the expressive proteomic approach to elucidate the molecular basis. We further selected 12 differentially expressed proteins in CTGF-induced hESC-derived mesenchymal stem cells (C-hESC-MSCs), which were found to be involved in the metabolic process, immune response, cell signaling, and cell proliferation, as compared to bone marrow derived-MSCs(BM-MSCs). Moreover, these up-regulated proteins were potentially related to the Wnt/β-catenin pathway. These results suggest that C-hESC-MSCs are a highly proliferative cell population, which can interact with the Wnt/β-catenin signaling pathway; thus, due to the upregulated cell survival ability or downregulated apoptosis effects of C-hESC-MSCs, these can be used as an unlimited cellular source in the cell therapy field for a higher therapeutic potential. Overall, the study provided valuable insights into the molecular functioning of hESC derivatives as a valuable cellular source.

• 생명과학회지
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• 제23권7호
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• pp.947-954
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• 2013

Wnt/${\beta}$-catenin 신호는 세포의 운명 결정, 증식, 분화 등을 조절하는 척추 동물 배아 발생과 성체의 항상성 유지에 필수적인 세포신호전달경로이다. 이러한 Wnt/${\beta}$-catenin의 비정상적인 조절에 의해 선천적 기형, 암, 대사질환 등을 비롯한 다양한 질병이 유발된다. 이를 바탕으로 최근 Wnt/${\beta}$-catenin 신호의 조절을 통한 암을 비롯한 질병의 치료를 위한 연구가 활발히 진행되고 있다. 따라서 Wnt/${\beta}$-catenin 신호를 조절하는 인자의 발굴 및 자세한 작용 기전에 대한 연구가 절실히 필요하다. 본 총설에서는 최근 새롭게 알려진 Wnt/${\beta}$-catenin 신호 조절 기작에 대해 설명하고, 현재까지 알려진 Wnt/${\beta}$조절하는 인산화 효소(kinase)의 종류와 작용 기전과 새로운 약물 타겟으로 전망을 알아 보고자 한다.

• Journal of Microbiology and Biotechnology
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• 제34권4호
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• pp.812-827
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• 2024

Phloroglucinol (PG) is one of the abundant isomeric benzenetriols in brown algae. Due to its polyphenolic structure, PG exhibits various biological activities. However, the impact of PG on anagen signaling and oxidative stress in human dermal papilla cells (HDPCs) is unknown. In this study, we investigated the therapeutic potential of PG for improving hair loss. A non-cytotoxic concentration of PG increased anagen-inductive genes and transcriptional activities of β-Catenin. Since several anagen-inductive genes are regulated by β-Catenin, further experiments were performed to elucidate the molecular mechanism by which PG upregulates anagen signaling. Various biochemical analyses revealed that PG upregulated β-Catenin signaling without affecting the expression of Wnt. In particular, PG elevated the phosphorylation of protein kinase B (AKT), leading to an increase in the inhibitory phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at serine 9. Treatment with the selective phosphoinositide 3-kinase/AKT inhibitor, LY294002, restored the increased AKT/GSK3β/β-Catenin signaling and anagen-inductive proteins induced by PG. Moreover, conditioned medium from PG-treated HDPCs promoted the proliferation and migration of human epidermal keratinocytes via the AKT signaling pathway. Subsequently, we assessed the antioxidant activities of PG. PG ameliorated the elevated oxidative stress markers and improved the decreased anagen signaling in hydrogen peroxide (H₂O₂)-induced HDPCs. The senescence-associated β-galactosidase staining assay also demonstrated that the antioxidant abilities of PG effectively mitigated H₂O₂-induced senescence. Overall, these results indicate that PG potentially enhances anagen signaling and improves oxidative stress-induced cellular damage in HDPCs. Therefore, PG can be employed as a novel therapeutic component to ameliorate hair loss symptoms.