• Title/Summary/Keyword: Molecular pathway

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A New Insight of Salt Stress Signaling in Plant

  • Park, Hee Jin;Kim, Woe-Yeon;Yun, Dae-Jin
    • Molecules and Cells
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    • v.39 no.6
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    • pp.447-459
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    • 2016
  • Many studies have been conducted to understand plant stress responses to salinity because irrigation-dependent salt accumulation compromises crop productivity and also to understand the mechanism through which some plants thrive under saline conditions. As mechanistic understanding has increased during the last decades, discovery-oriented approaches have begun to identify genetic determinants of salt tolerance. In addition to osmolytes, osmoprotectants, radical detoxification, ion transport systems, and changes in hormone levels and hormone-guided communications, the Salt Overly Sensitive (SOS) pathway has emerged to be a major defense mechanism. However, the mechanism by which the components of the SOS pathway are integrated to ultimately orchestrate plant-wide tolerance to salinity stress remains unclear. A higher-level control mechanism has recently emerged as a result of recognizing the involvement of GIGANTEA (GI), a protein involved in maintaining the plant circadian clock and control switch in flowering. The loss of GI function confers high tolerance to salt stress via its interaction with the components of the SOS pathway. The mechanism underlying this observation indicates the association between GI and the SOS pathway and thus, given the key influence of the circadian clock and the pathway on photoperiodic flowering, the association between GI and SOS can regulate growth and stress tolerance. In this review, we will analyze the components of the SOS pathways, with emphasis on the integration of components recognized as hallmarks of a halophytic lifestyle.

Functional Gene Analysis to Identify Potential Markers Induced by Benzene in Two Different Cell Lines, HepG2 and HL-60

  • Kim, Youn-Jung;Song, Mi-Kyung;Sarma, Sailendra Nath;Choi, Han-Saem;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.4 no.3
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    • pp.183-191
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    • 2008
  • Volatile organic compounds (VOCs) are common constituents of cleaning and degreasing agents, paints, pesticides, personal care products, gasoline and solvents. And VOCs are evaporated at room temperature and most of them exhibit acute and chronic toxicity to human. Benzene is the most widely used prototypical VOC and the toxic mechanisms of them are still unclear. The multi-step process of toxic mechanism can be more fully understood by characterizing gene expression changes induced in cells by toxicants. In this study, DNA microarray was used to monitor the expression levels of genes in HepG2 cells and HL-60 cells exposed to the benzene on IC20 and IC50 dose respectively. In the clustering analysis of gene expression profiles, although clusters of HepG2 and HL-60 cells by benzene were divided differently, expression pattern of many genes observed similarly. We identified 916 up-regulated genes and 1,144 down-regulated genes in HepG2 cells and also 1,002 up-regulated genes and 919 down-regulated genes in HL-60 cells. The gene ontology analysis on genes expressed by benzene in HepG2 and HL-60 cells, respectively, was performed. Thus, we found some principal pathways, such as, focal adhesion, gap junction and signaling pathway in HepG2 cells and toll-like receptor signaling pathway, MAPK signaling pathway, p53 signaling pathway and neuroactive ligand-receptor interaction in HL-60 cells. And we also found 16 up-regulated and 14 down-regulated commonly expressed total 30 genes that belong in the same biological process like inflammatory response, cell cycle arrest, cell migration, transmission of nerve impulse and cell motility in two cell lines. In conclusion, we suggest that this study is meaningful because these genes regarded as strong potential biomarkers of benzene independent of cell type.

Effect of Citrus macroptera Fruit Pulp Juice on Alteration of Caspase Pathway Rendering Anti-Proliferative Activity against Ehrlich's Ascites Carcinoma in Mice

  • Hasan, Md. Mahmudul;Islam, Md. Shihabul;Hoque, Kazi Md. Faisal;Haque, Ariful;Reza, Md Abu
    • Toxicological Research
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    • v.35 no.3
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    • pp.271-277
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    • 2019
  • Citrus macroptera (Rutaceae) has long been used in folk medicine in Bangladesh. Considering the folkloric context, this study was aimed to scrutinize anti-proliferative activity of C. macroptera fruit pulp juice (CMFPJ) against Ehrlich's ascites carcinoma (EAC). The anti-proliferative capacity of CMFPJ was investigated and confirmed primarily using MTT assay. In vivo anti-proliferative aptitude of CMFPJ was investigated with 25, 50, and 100 mg/kg/day intraperitoneal (i.p.) treatment. Anti-proliferative efficacy of CMFPJ was assessed based on EAC growth inhibition. CMFPJ inhibited EAC growth in vitro in a dose-dependent manner. And the percentages of in vivo EAC growth inhibition were 19.53, 49.2, and 68.9% at 25, 50, and 100 mg/kg CMFPJ respectively. CMFPJ significantly induced expression of apoptosis regulatory genes caspase-8, caspase-9, cytochrome-c, and caspase-3. This considerable anti-cancer activity was perhaps due to combinatorial effect of lectin, polyphenols, and flavonoids present in CMFPJ.

Identification of ERBB pathway-activated cells in triple-negative breast cancer

  • Cho, Soo Young
    • Genomics & Informatics
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    • v.17 no.1
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    • pp.3.1-3.4
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    • 2019
  • Intratumor heterogeneity within a single tumor mass is one of the hallmarks of malignancy and has been reported in various tumor types. The molecular characterization of intratumor heterogeneity in breast cancer is a significant challenge for effective treatment. Using single-cell RNA sequencing (RNA-seq) data from a public resource, an ERBB pathway activated triple-negative cell population was identified. The differential expression of three subtyping marker genes (ERBB2, ESR1, and PGR) was not changed in the bulk RNA-seq data, but the single-cell transcriptomes showed intratumor heterogeneity. This result shows that ERBB signaling is activated using an indirect route and that the molecular subtype is changed on a single-cell level. Our data propose a different view on breast cancer subtypes, clarifying much confusion in this field and contributing to precision medicine.

Identification and Characterization of Thermoplasma acidophilum 2-Keto-3-Deoxy-D-Gluconate Kinase: A New Class of Sugar Kinases

  • Jung, Jin-Hwa;Lee, Sun-Bok
    • Biotechnology and Bioprocess Engineering:BBE
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    • v.10 no.6
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    • pp.535-539
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    • 2005
  • The thermoacidophilic archaeon Thermoplasma acidophilum has long been known to utilize D-glucose via the non-phosphorylated Entner-Doudoroff (nED) pathway. We now report the identification of a gene encoding 2-keto-3-deoxy-D-gluconate (KDG) kinase. The discovery of this gene implies the presence of a glycolysis pathway, other than the nED pathway. It was found that Ta0122 in the T. acidophilum genome corresponded to KDG kinase. This enzyme shares no similarity with known KDG kinases, and belongs to a novel class of sugar kinases. Of the five sugars tested only KDG was utilized as a substrate.

pH Response Pathways in Fungi: Adapting to Host-derived and Environmental Signals

  • Selvig, Kyla;Alspaugh, J. Andrew
    • Mycobiology
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    • v.39 no.4
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    • pp.249-256
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    • 2011
  • Microorganisms are significantly affected when the ambient pH of their environment changes. They must therefore be able to sense and respond to these changes in order to survive. Previous investigators have studied various fungal species to define conserved pH-responsive signaling pathways. One of these pathways, known as the Pal/Rim pathway, is activated in response to alkaline pH signals, ultimately targeting the PacC/Rim101 transcription factor. Although the central signaling components are conserved among divergent filamentous and yeast-like fungi, there is some degree of signaling specificity between fungal species. This specificity exists primarily in the downstream transcriptional targets of this pathway, likely allowing differential adaptation to species-specific environmental niches. In this review, the role of the Pal/Rim pathway in fungal pH response is discussed. Also highlighted are functional differences present in this pathway among human fungal pathogens, differences that allow these specialized microorganisms to survive in the various micro-environments of the infected human host.

Role of MAPK Signaling Pathways in Regulating the Hydrophobin Cryparin in the Chestnut Blight Fungus Cryphonectria parasitica

  • So, Kum-Kang;Kim, Dae-Hyuk
    • Mycobiology
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    • v.45 no.4
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    • pp.362-369
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    • 2017
  • We assessed the regulation of cryparin, a class II hydrophobin, using three representative mitogen-activated protein kinase (MAPK) pathways in Cryphonectria parasitica. Mutation of the CpSlt2 gene, an ortholog of yeast SLT2 in the cell wall integrity (CWI) pathway, resulted in a dramatic decrease in cryparin production. Similarly, a mutant of the CpBck1 gene, a MAP kinase kinase kinase gene in the CWI pathway, showed decreased cryparin production. Additionally, mutation of the cpmk1 gene, an ortholog of yeast HOG1, showed decreased cryparin production. However, mutation of the cpmk2 gene, an ortholog of yeast Kss1/Fus3, showed increased cryparin production. The easy-wet phenotype and accumulation of the cryparin transcript in corresponding mutants were consistent with the cryparin production results. In silico analysis of the promoter region of the cryparin gene revealed the presence of binding motifs related to downstream transcription factors of CWI, HOG1, and pheromone responsive pathways including MADS-box- and Ste12-binding domains. Real-time reverse transcriptase PCR analyses indicated that both CpRlm1, an ortholog of yeast RLM1 in the CWI pathway, and cpst12, an ortholog of yeast STE12 in the mating pathway, showed significantly reduced transcription levels in the mutant strains showing lower cryparin production in C. prasitica. However, the transcription of CpMcm1, an ortholog of yeast MCM1, did not correlate with that of the mutant strains showing downregulation of cryparin. These results indicate that three representative MAPK pathways played a role in regulating cryparin production. However, regulation varied depending on the MAPK pathways: the CWI and HOG1 pathways were stimulatory, whereas the pheromone-responsive MAPK was repressive.

Functional Conservation and Divergence of FVE Genes that Control Flowering Time and Cold Response in Rice and Arabidopsis

  • Baek, Il-Sun;Park, Hyo-Young;You, Min Kyoung;Lee, Jeong Hwan;Kim, Jeong-Kook
    • Molecules and Cells
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    • v.26 no.4
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    • pp.368-372
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    • 2008
  • Recent molecular and genetic studies in rice, a short-day plant, have elucidated both conservation and divergence of photoperiod pathway genes and their regulators. However, the biological roles of rice genes that act within the autonomous pathway are still largely unknown. In order to better understand the function of the autonomous pathway genes in rice, we conducted molecular genetic analyses of OsFVE, a rice gene homologous to Arabidopsis FVE. OsFVE was found to be ubiquitously expressed in vegetative and reproductive organs. Overexpression of OsFVE could rescue the flowering time phenotype of the Arabidopsis fve mutants by up-regulating expression of the SUPPRESSOR OF OVEREXPRESSION OF CO1 (SOC1) and down-regulating FLOWERING LOCUS C (FLC) expression. These results suggest that there may be a conserved function between OsFVE and FVE in the control of flowering time. However, OsFVE overexpression in the fve mutants did not rescue the flowering time phenotype in in relation to the response to intermittent cold treatment.

P53 transcription-independent activity mediates selenite-induced acute promyelocytic leukemia NB4 cell apoptosis

  • Guan, Liying;Huang, Fang;Li, Zhushi;Han, Bingshe;Jiang, Qian;Ren, Yun;Yang, Yang;Xu, Caimin
    • BMB Reports
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    • v.41 no.10
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    • pp.745-750
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    • 2008
  • Selenium, an essential trace element possessing anti-carcinogenic properties, can induce apoptosis in cancer cells. We have previously shown that sodium selenite can induce apoptosis by activating the mitochondrial apoptosis pathway in NB4 cells. However, the detailed mechanism remains unclear. Presently, we demonstrate that p53 contributes to apoptosis by directing signaling at the mitochondria. Immunofluorescent and Western blot procedures revealed selenite-induced p53 translocation to mitochondria. Inhibition of p53 blocked accumulation of reactive oxygen species (ROS) and loss of mitochondrial membrane potential, suggesting that mitochondrial p53 acts as an upstream signal of ROS and activates the mitochondrial apoptosis pathway. Selenite also disrupted cellular calcium ion homeostasis in a ROS-dependent manner and increased mitochondrial calcium ion concentration. p38 kinase mediated phosphorylation and mitochondrial translocation of p53. Taken together, these results indicate that p53 involves selenite-induced NB4 cell apoptosis by translocation to mitochondria and activation mitochondrial apoptosis pathway in a transcription-independent manner.

Non-Polar Myxococcus fulvus KYC4048 Metabolites Exert Anti-Proliferative Effects via Inhibition of Wnt/β-Catenin Signaling in MCF-7 Breast Cancer Cells

  • Park, Juha;Yoo, Hee-Jin;Yu, Ah-Ran;Kim, Hye Ok;Park, Sang Cheol;Jang, Young Pyo;Lee, Chayul;Choe, Wonchae;Kim, Sung Soo;Kang, Insug;Yoon, Kyung-Sik
    • Journal of Microbiology and Biotechnology
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    • v.31 no.4
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    • pp.540-549
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    • 2021
  • The Wnt/β-catenin signaling pathway is involved in breast cancer and Myxococcus fulvus KYC4048 is a myxobacterial strain that can produce a variety of bioactive secondary metabolites. Although a previous study revealed that KYC4048 metabolites exhibit anti-proliferative effects on breast cancer, the biochemical mechanism involved in their effects remains unclear. In the present study, KYC4048 metabolites were separated into polar and non-polar (ethyl acetate and n-hexane) fractions via liquid-liquid extraction. The effects of these polar and non-polar KYC4048 metabolites on the viability of breast cancer cells were then determined by MTT assay. Expression levels of Wnt/β-catenin pathway proteins were determined by Western blot analysis. Cell cycle and apoptosis were measured via fluorescence-activated cell sorting (FACS). The results revealed that non-polar KYC4048 metabolites induced cell death of breast cancer cells and decreased expression levels of WNT2B, β-catenin, and Wnt target genes (c-Myc and cyclin D1). Moreover, the n-hexane fraction of non-polar KYC4048 metabolites was found most effective in inducing apoptosis, necrosis, and cell cycle arrest, leading us to conclude that it can induce apoptosis of breast cancer cells through the Wnt/β-catenin pathway. These findings provide evidence that the n-hexane fraction of non-polar KYC4048 metabolites can be developed as a potential therapeutic agent for breast cancer via inhibition of the Wnt/β-catenin pathway.