• Title/Summary/Keyword: signal pathways

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Regulation of Blastocyst Differentiation by the Serial Exposure of Conconavalin A and $PGE_2$ (Concanavalin A와 $PGE_2$의 순차적 노출에 의한 포배의 분화 조절)

  • Cheon, Yong Pil
    • Development and Reproduction
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    • v.12 no.3
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    • pp.267-274
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    • 2008
  • Differentiation of blastocyst is critical step for implantation and is under the control of regulation factors originated from embryo or reproductive tracts. The sequential communication with those factors is suspected as critical events for differentiation. It has been suggested that intracellular signaling pathways activated by calcium is essential in differentiation of blastocyst. Previously, it was known that concanavalin A (Con A) increase the levels of free calcium in blastocyst stage. However, Con A can not accelerate the hatching, although heparin-binding epidermal growth factor-like growth factor (HB-EGF), a modulator of calcium level, accelerate the hatching of blastocyst. In this study, it was investigated whether Con A or prostaglandin $E_2$ ($PGE_2$) can modulate the differentiation of blastocyst. Con A accelerated the expansion of blastocyst in both 1 hr pulse treatment group and continuous treatment group. However, Con A significantly suppressed the hatching in both groups. The inhibition was significantly strong in continuous treatment group compared with 1 hr pulse treatment group. On the other hand, $PGE_2$ induced the increase the free calcium level, but did not accelerate the expansion. In addition $10{\mu}m\;PGE_2$ inhibited hatching. However, $PGE_2$ could accelerate hatching in Con A pretreated blastocyst. $PGE_2$ also caused the increase of free calcium level in Con A pretreated blastocyst. From these results, it is suggested that changes of the free calcium level induce a different calcium-mediated signaling pathways. In addition, sequential stimulation by signal molecules may triggers the cellular mechanisms for the differentiation of blastocyst.

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Initial Characterization of yliH in Salmonella typhimurium

  • Park, Kyung-Hwa;Song, Mi-Ryung;Choy, Hyon-E.
    • Journal of Microbiology
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    • v.45 no.6
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    • pp.558-565
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    • 2007
  • Using microarray analysis, we determined those Salmonella genes induced at the entry of stationary phase, and subsequently discovered that uncharacterized yliH was induced most dramatically. We set out to establish the molecular mechanism underlying the stationary phase induction of yliH under the standard culture condition, LB with vigorous aeration, by analyzing its promoter activity in various mutant backgrounds, lacking stationary phase ${\sigma}$, $RpoS^-$, or stringent signal molecules ppGpp, ${\Delta}relA$ ${\Delta}spoT$. It was found that the stationary phase induction of yliHp was partially dependent on rpoS but entirely dependent on ppGpp. DNA sequence analysis revealed that the Salmonella yliH gene is composed of 381 base-pair nucleotides, with overall amino acid sequence revealing 76.38% amino acid identity and 88.98% similarity with Escherichia coli yliH, although no motif from data base was noted for its possible role. Recently however, it has been reported that yliH in E. coli was implicated in biofilm formation and motility by repressing these activities (Domka et al., 2006). We have constructed a mutant Salmonella deleting yliH gene by allele replacement and examined its phenotype, and found that the yliH in Salmonella more or less affects motility and adherence by enhancing these activities. The effect on biofilm formation in Salmonella was uncertain. Moreover, addition of cloned yliH of E. coli into Salmonella did not reduce motility or adherence. Taken together, it appears that the pathways implicating yliH for biofilm formation and motility in E. coli and in Salmonella are somewhat different.

Protein Kinase C Activates ATP-sensitive Potassium Channels in Rabbit Ventricular Myocytes

  • Kim, Na-Ri;Youm, Jae-Boum;Joo, Hyun;Kim, Hyung-Kyu;Kim, Eui-Yong;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.9 no.4
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    • pp.187-193
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    • 2005
  • Several signal transduction pathways have been implicated in ischemic preconditioning induced by the activation of ATP-sensitive $K^+$ $(K_{ATP})$ channels. We examined whether protein kinase C (PKC) modulated the activity of $K_{ATP}$ channels by recording $K_{ATP}$ channel currents in rabbit ventricular myocytes using patch-clamp technique and found that phorbol 12,13-didecanoate (PDD) enhanced pinacidil-induced $K_{ATP}$ channel activity in the cell-attached configuration; and this effect was prevented by bisindolylmaleimide (BIM). $K_{ATP}$ channel activity was not increased by $4{\alpha}-PDD$. In excised insideout patches, PKC stimulated $K_{ATP}$ channels in the presence of 1 mM ATP, and this effect was abolished in the presence of BIM. Heat-inactivated PKC had no effect on channel activity. PKC-induced activation of $K_{ATP}$ channels was reversed by PP2A, and this effect was not detected in the presence of okadaic acid. These results suggest that PKC activates $K_{ATP}$ channels in rabbit ventricular myocytes.

Stanniocalcin 2 enhances mesenchymal stem cell survival by suppressing oxidative stress

  • Kim, Pyung-Hwan;Na, Sang-Su;Lee, Bomnaerin;Kim, Joo-Hyun;Cho, Je-Yoel
    • BMB Reports
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    • v.48 no.12
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    • pp.702-707
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    • 2015
  • To overcome the disadvantages of stem cell-based cell therapy like low cell survival at the disease site, we used stanniocalcin 2 (STC2), a family of secreted glycoprotein hormones that function to inhibit apoptosis and oxidative damage and to induce proliferation. STC2 gene was transfected into two kinds of stem cells to prolong cell survival and protect the cells from the damage by oxidative stress. The stem cells expressing STC2 exhibited increased cell viability and improved cell survival as well as elevated expression of the pluripotency and self-renewal markers (Oct4 and Nanog) under sub-lethal oxidative conditions. Up-regulation of CDK2 and CDK4 and down-regulation of cell cycle inhibitors p16 and p21 were observed after the delivery of STC2. Furthermore, STC2 transduction activated pAKT and pERK 1/2 signal pathways. Taken together, the STC2 can be used to enhance cell survival and maintain long-term stemness in therapeutic use of stem cells.

Valproic Acid Induces Transcriptional Activation of Human GD3 Synthase (hST8Sia I) in SK-N-BE(2)-C Human Neuroblastoma Cells

  • Kwon, Haw-Young;Dae, Hyun-Mi;Song, Na-Ri;Kim, Kyoung-Sook;Kim, Cheorl-Ho;Lee, Young-Choon
    • Molecules and Cells
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    • v.27 no.1
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    • pp.113-118
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    • 2009
  • In this study, we have shown the transcriptional regulation of the human GD3 synthase (hST8Sia I) induced by valproic acid (VPA) in human neuroblastoma SK-N-BE(2)-C cells. To elucidate the mechanism underlying the regulation of hST8Sia I gene expression in VPA-stimulated SK-N-BE(2)-C cells, we characterized the promoter region of the hST8Sia I gene. Functional analysis of the 5'-flanking region of the hST8Sia I gene by the transient expression method showed that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-${\kappa}B$, functions as the VPA-inducible promoter of hST8Sia I in SK-N-BE(2)-C cells. Site-directed mutagenesis and electrophoretic mobility shift assay indicated that the NF-${\kappa}B$ binding site at -731 to -722 was crucial for the VPA-induced expression of hST8Sia I in SK-N-BE(2)-C cells. In addition, the transcriptional activity of hST8Sia I induced by VPA in SK-N-BE(2)-C cells was strongly inhibited by SP600125, which is a c-Jun N-terminal kinase (JNK) inhibitor, and $G{\ddot{O}}6976$, which is a protein kinase C (PKC) inhibitor, as determined by RT-PCR (reverse transcription-polymerase chain reaction) and luciferase assays. These results suggest that VPA markedly modulated transcriptional regulation of hST8Sia I gene expression through PKC/JNK signal pathways in SK-N-BE(2)-C cells.

Indole-3-Carbinol Promotes Goblet-Cell Differentiation Regulating Wnt and Notch Signaling Pathways AhR-Dependently

  • Park, Joo-Hung;Lee, Jeong-Min;Lee, Eun-Jin;Hwang, Won-Bhin;Kim, Da-Jeong
    • Molecules and Cells
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    • v.41 no.4
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    • pp.290-300
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    • 2018
  • Using an in vitro model of intestinal organoids derived from intestinal crypts, we examined effects of indole-3-carbinol (I3C), a phytochemical that has anticancer and aryl hydrocarbon receptor (AhR)-activating abilities and thus is sold as a dietary supplement, on the development of intestinal organoids and investigated the underlying mechanisms. I3C inhibited the in vitro development of mouse intestinal organoids. Addition of ${\alpha}$-naphthoflavone, an AhR antagonist or AhR siRNA transfection, suppressed I3C function, suggesting that I3C-mediated interference with organoid development is AhR-dependent. I3C increased the expression of Muc2 and lysozyme, lineage-specific genes for goblet cells and Paneth cells, respectively, but inhibits the expression of IAP, a marker gene for enterocytes. In the intestines of mice treated with I3C, the number of goblet cells was reduced, but the number of Paneth cells and the depth and length of crypts and villi were not changed. I3C increased the level of active nonphosphorylated ${\beta}$-catenin, but suppressed the Notch signal. As a result, expression of Hes1, a Notch target gene and a transcriptional repressor that plays a key role in enterocyte differentiation, was reduced, whereas expression of Math1, involved in the differentiation of secretory lineages, was increased. These results provide direct evidence for the role of AhR in the regulation of the development of intestinal stem cells and indicate that such regulation is likely mediated by regulation of Wnt and Notch signals.

Gene Expression Profiles of HeLa Cells Impacted by Hepatitis C Virus Non-structural Protein NS4B

  • Zheng, Yi;Ye, Lin-Bai;Liu, Jing;Jing, Wei;Timani, Khalid A.;Yang, Xiao-Jun;Yang, Fan;Wang, Wei;Gao, Bo;Wu, Zhen-Hui
    • BMB Reports
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    • v.38 no.2
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    • pp.151-160
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    • 2005
  • By a cDNA array representing 2308 signal transduction related genes, we studied the expression profiles of HeLa cells stably transfected by Hepatitis C virus nonstructural protein 4B (HCV-NS4B). The alterations of the expression of four genes were confirmed by real-time quantitative RT-PCR; and the aldo-keto reductase family 1, member C1 (AKR1C1) enzyme activity was detected in HCV-NS4B transiently transfected HeLa cells and Huh-7, a human hepatoma cell line. Of the 2,308 genes we examined, 34 were up-regulated and 56 were down-regulated. These 90 genes involved oncogenes, tumor suppressors, cell receptors, complements, adhesions, transcription and translation, cytoskeletion and cellular stress. The expression profiling suggested that multiple regulatory pathways were affected by HCV-NS4B directly or indirectly. And since these genes are related to carcinogenesis, host defense system and cell homeostatic mechanism, we can conclude that HCV-NS4B could play some important roles in the pathogenesis mechanism of HCV.

Post-transcriptional Regulation of Gcn5, a Putative Regulator of Hox in Mouse Embryonic Fibroblast Cells

  • Lee, You-Ra;Oh, Ji-Hoon;Kong, Kyoung-Ah;Kim, Myoung-Hee
    • Biomedical Science Letters
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    • v.18 no.2
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    • pp.165-168
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    • 2012
  • Hox proteins containing DNA-binding homedomain act as transcription factors important for anteroposterior body patterning during vertebrate embryogenesis. However, the precise mechanisms by which signal pathways are transduced to regulate the Hox gene expression are not clear. In the course of an attempt to isolate an upstream regulatory factor(s) controlling Hox genes, protein kinase B alpha (Akt1) has been identified as a putative regulator of Hox genes through in silico analysis (GEO profile). In the Gene Expression Omnibus (GEO) dataset GDS1784 at the NCBI (National Center for Biotechnology Information) site, Hox genes were differentially expressed depending on the presence or absence of Akt1. Since it was not well known how Akt1 regulates the specific Hox genes, whose transcription was reported to be regulated by epigenetic modifications such as histone acetylation, methylation etc., the expression of Gcn5, a histone acetyltransferase (HAT), was analyzed in wild type (WT) as well as in $Akt1^{-/-}$ mouse embryonic fibroblast (MEF) cells. RT-PCR analysis revealed that the amount of Gcn5 mRNA was similar in both WT and $Akt1^{-/-}$ MEFs. However, the protein level of Gcn5 was significantly increased in $Akt1^{-/-}$ MEF cells. The half life of Gcn5 was 1 hour in wild type whereas 8 hours in $Akt1^{-/-}$ MEF. These data all together, indicate that Gcn5 is post-transcriptionally down-regulated and the protein stability is negatively regulated by Akt1 in MEF cells.

Effects on Inhibition of Angiogenesis in MCF-7 Cells by the Aqueous Root Extract of Ailanthus Altissima (저근백피 추출물이 유선암 세포에서의 신생혈관 미치는 영향)

  • Jeong Ji Hak;Yun Young Gab;Jeon Byung Hun;Park Hae Ryoun;An Won Gun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1613-1616
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    • 2004
  • The cellular response to hypoxia is controlled to a large degree by the transcription factor Hypoxia-inducible factor-1(HIF-1). HIF-1 is a transcription factor that is activated by hypoxia and plays a critical role in the development of the cancer phenotype. HIF-1 regulates transcription of a number of genes crucial for tumor survival under hypoxic conditions, including vascular endothelial growth factor(VEGF), erythropoietin(Epo) and several glycolytic enzymes. Tumors in which hypoxia can not induce HIF-1 transcriptional activity remain small and fail to metastasize. In this study, we examined whether aqueous root extract of Ailanthus altissima (REA) downregulate HIF-1, VEGF and p53, and raise the possibility that depletion of these proteins and the anti proliferative activities of REA have any effects on inhibition of angiogenesis in MCF-7 cells. Pharmacologic targeting of specific signal transduction pathways related to oncogenic transformation is a promising approach in cancer treatment. Therefore, REA could be a candidate drug for further clinical development.

Aloe-Emodin Induces Chondrogenic Differentiation of ATDC5 Cells via MAP Kinases and BMP-2 Signaling Pathways

  • Yang, Ming;Li, Liang;Heo, Seok-Mo;Soh, Yunjo
    • Biomolecules & Therapeutics
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    • v.24 no.4
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    • pp.395-401
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    • 2016
  • Endochondral bone formation is the process by which mesenchymal cells condense into chondrocytes, which are ultimately responsible for new bone formation. The processes of chondrogenic differentiation and hypertrophy are critical for bone formation and are therefore highly regulated. The present study was designed to investigate the effect of aloe-emodin on chondrogenic differentiation in clonal mouse chondrogenic ATDC5 cells. Aloe-emodin treatment stimulated the accumulation of cartilage nodules in a dose-dependent manner. ATDC5 cells were treated with aloe-emodin and stained with alcian blue. Compared with the control cells, the ATDC5 cells showed more intense alcian blue staining. This finding suggested that aloe-emodin induced the synthesis of matrix proteoglycans and increased the activity of alkaline phosphatase. Aloe-emodin also enhanced the expressions of chondrogenic marker genes such as collagen II, collagen X, BSP and RunX2 in a time-dependent manner. Furthermore, examination of the MAPK signaling pathway showed that aloe-emodin increased the activation of extracellular signal-regulated kinase (ERK), but had no effect on p38 and c-jun N-terminal kinase (JNK). Aloe-emodin also enhanced the protein expression of BMP-2 in a time-dependent manner. Thus, these results showed that aloe-emodin exhibited chodromodulating effects via the BMP-2 or ERK signaling pathway. Aloe-emodin may have potential future applications for the treatment of growth disorders.