• Title/Summary/Keyword: activating transcription factor 6

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Immunohistochemical Expressions of Sodium/Iodide Symporter (NIS) and Thyroid Transcription Factor-l (TTF-1) and Their Relationship in Primary Pulmonary Adenocarcinoma

  • Lee Kyung-Eun;Kang Do-Young;Choi Phil-Jo;Hong Young-Seoub;Roh Mee-Sook;Shon Jae-Jeong;Lee Jung-Min;Hwang Soo-Myoung
    • Biomedical Science Letters
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    • v.12 no.3
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    • pp.171-176
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    • 2006
  • Sodium iodide symporter (NIS) plays a key role in thyroid hormone production by efficiently accumulating iodide from the circulating blood into the thyocytes, and this is done against an electrochemical gradient. Thyroid transcription factor-l (TTF-l) is a homeodomain-containing protein expressed in embryonic diencephalons, thyroid, and lung and has been found to bind to thyroid specific promoters and to activate their transcriptional activity. TTF-l may be one of the factors capable of activating NIS gene expression in the thyroid gland, thus it accounts for the lower levels of NIS gene expression that are seen in the extrathyroidal tissues. However, a high frequency of TTF-l expression has been observed, especially in primary lung adenocarcinoma. The present study was undertaken in order to elucidate the relationship between the expression of NIS and TTF-l in primary lung adenocarcinoma. Immunohistochemical studies for NIS and TTF-l were performed in 64 primary lung adenocarcinomas. Immunoreactivities for NIS and TTF-l were found in 49 (76.6%) and 45 (70.3%) out of 64 cases, respectively. Forty-one (83.7%) of the 49 cases with positive NIS immunoreactivity showed positive TTF-l expression, whereas 11 (73.3%) of the 15 cases with negative NIS immunoreactivity showed negative TTF-l expression (P<0.05). So the NIS expression was significantly associated with the TTF-l expression. These findings suggest that TTF-l may be one of the factors capable of activating NIS gene expression in primary lung adenocarcinoma. Further studies are needed to define the relation between NIS and TTF-l for examining the mechanisms of tissue-specific NIS expression.

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4-phenylbutyric Acid Regulates Collagen Synthesis and Secretion Induced by High Concentrations of Glucose in Human Gingival Fibroblasts

  • Lee, Geum-Hwa;Oh, Hyo-Won;Lim, Hyun-Dae;Lee, Wan;Chae, Han-Jung;Kim, Hyung-Ryong
    • The Korean Journal of Physiology and Pharmacology
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    • v.15 no.6
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    • pp.345-351
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    • 2011
  • High glucose leads to physio/pathological alterations in diabetes patients. We investigated collagen production in human gingival cells that were cultured in high concentrations of glucose. Collagen synthesis and secretion were increased when the cells were exposed to high concentrations of glucose. We examined endoplasmic reticulum (ER) stress response because glucose metabolism is related to ER functional status. An ER stress response including the expression of glucose regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), inositol requiring enzyme alpha (IRE-$1{\alpha}$) and phosphoreukaryotic initiation factor alpha (p-eIF-$2{\alpha}$) was activated in the presence of high glucose. Activating transcription factor 4 (ATF-4), a downstream protein of p-eIF-$2{\alpha}$ as well as a transcription factor for collagen, was also phosphorylated and translocalized into the nucleus. The chemical chaperone 4-PBA inhibited the ER stress response and ATF-4 phosphorylation as well as nuclear translocation. Our results suggest that high concentrations of glucose-induced collagen are linked to ER stress and the associated phosphorylation and nuclear translocation of ATF-4.

Isolation and Identification of Three Pseudomonas koreensis Strains with Anti-microbial Activities Producing Inducers of the Expression of Egr-1 Gene (Egr-1 유전자의 발현 유도물질을 생산하는 항균성 저 영양 세균의 분리 및 동정)

  • Yoon, Sang-Hong;Kim, Dong-Gwan;Lee, Young-Han;Shin, Soon-Young;Kwon, Soon-Woo;Lee, Chang-Muk;Kang, Han-Chul;Koo, Bon-Sung
    • Microbiology and Biotechnology Letters
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    • v.39 no.2
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    • pp.119-125
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    • 2011
  • The Egr-1 gene is known to be a transcription factor for activating the expression of many tumor-repressing genes. In this study, three strains activating the promoter of the Egr-1 gene were selected, through the use of Egr-1 luciferase reporter assay and western blotting, from amongst approximately 3,800 oligotrophic bacteria isolated from the cultivated soils of various regions within Korea. These strains were identified as Pseudomonas koreensis on the basis of phylogenetic tree analysis of their 16S ribosomal DNA sequences and biochemical characteristics analyses using a variety of commercial kits (API 20NE, ID 32GN, API ZYM kits). In addition, we discovered that these strains produced anti-bacterial activity against Bacillus subtilis, Staphylococcus aureus and Listeria monocytogenes.

Anti-Melanogenic Activities of Ranunculus chinensis Bunge via ERK1/2-Mediated MITF Downregulation

  • Min-Jin Kim;Yong Tae Jeong;Buyng Su Hwang;Yong Hwang;Dae Won Jeong;Yeong Taek Oh
    • Korean Journal of Plant Resources
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    • v.35 no.6
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    • pp.704-712
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    • 2022
  • Research on whitening materials using natural alternatives is actively being conducted. The aim of this study was to investigate the in vitro inhibitory effects of Ranunculus chinensis Bunge (RCB) on melanogenesis and associated enzymes, such as tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2 in B16F10 murine melanoma cells. We found that RCB extract significantly attenuated melanin synthesis and reduced the activity of intracellular tyrosinase, a rate-limiting melanogenic enzyme. Western blot analysis showed that RCB extract decreased the protein expression of tyrosinase and TRP-1. In addition, it significantly decreased the expression of microphthalmia-associated transcription factor (MITF), a key regulator of melanogenesis. Extracellular signal-regulated kinase (ERK) activation has been reported to be involved in the inhibition of melanogenesis. Thus, we investigated whether the hypopigmentary effects of RCB extract were related to the activation of ERK. RCB extract induced ERK phosphorylation in a dose-dependent manner. Furthermore, it markedly inhibited body pigmentation in a zebrafish model. Our results suggest that RCB extract inhibits melanogenesis by activating ERK pathway-mediated suppression of MITF and its downstream target genes, including tyrosinase. Therefore, RCB extract can be used as a whitening agent in the development of functional cosmetics.

Porcine parvovirus nonstructural protein NS1 activates NF-κB and it involves TLR2 signaling pathway

  • Jin, Xiaohui;Yuan, Yixin;Zhang, Chi;Zhou, Yong;Song, Yue;Wei, Zhanyong;Zhang, Gaiping
    • Journal of Veterinary Science
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    • v.21 no.3
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    • pp.50.1-50.16
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    • 2020
  • Background: Porcine parvovirus (PPV) is a single-stranded DNA virus that causes porcine reproductive failure. It is of critical importance to study PPV pathogenesis for the prevention and control of the disease. NS1, a PPV non-structural protein, is participated in viral DNA replication, transcriptional regulation, and cytotoxicity. Our previous research showed that PPV can activate nuclear factor kappa B (NF-κB) signaling pathway and then up-regulate the expression of interleukin (IL)-6. Objectives: Herein, the purpose of this study is to determine whether the non-structural protein NS1 of PPV also has the same function. Methods: Real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay, western blot, immunofluorescence assay and small interfering RNA (siRNA) were used. Results: Our findings demonstrated that PPV NS1 protein can up-regulate the expression levels of IL-6 and tumor necrosis factor-alpha in a dose-dependent manner. Moreover, PPV NS1 protein was found to induce the phosphorylation of IκBα, then leading to the phosphorylation and nuclear translocation of NF-κB. In addition, the NS1 protein activated the upstream pathways of NF-κB. Meanwhile, TLR2-siRNA assay showed TLR2 plays an important role in the activation of NF-κB signaling pathway induced by PPV-NS1. Conclusions: These findings indicated that PPV NS1 protein induced the up-regulated of IL-6 expression through activating the TLR2 and NF-κB signaling pathways. In conclusion, these findings provide a new avenue to study the innate immune mechanism of PPV infection.

The Effects of Astragali Radix Extracts on Mitochondrial Function in C2C12 Myotubes (C2C12 골격근세포에서 황기의 미토콘드리아 조절 작용)

  • Song, Miyoung
    • Journal of Korean Medicine for Obesity Research
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    • v.14 no.2
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    • pp.55-62
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    • 2014
  • Objective: The prevalence of metabolic syndrome and type 2 diabetes is increasing worldwide. Mitochondrial dysfunction is known to be involved in insulin resistance and obesity, researches have been increasing highly. Astragali Radix extract (ARE) or its main components have been shown to perform comparably to insulin by significantly reducing blood glucose levels in animal models however, the influence on mitochondrial dysfunction are not well understood. Methods: ARE (0.2, 0.5 and 1.0 mg/ml) or metformin (2.5 mM) were treated in C2C12 after 6 day-differentiation. The expressions of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and phosphorylation AMPK, peroxisome proliferators-activated receptror ${\gamma}$ coactivator $1{\alpha}$ ($PGC1{\alpha}$), nuclear respiratory factors 1 (NRF1), mitochondrial transcription factor (Tfam) and myosin heavy chain were detected with western blotting or polymerase chain reaction analysis. The morphological changes were also investigated. Results: ARE dose dependently increased phosphorylation of AMPK and respectively activated mRNA expressions of $PGC1{\alpha}$, NRF1 and Tfam which are mitochondrial biogenesis regulators. Furthermore, there were some morphologic differences of differentiated cells between ARE treatment and control. Conclusions: This study suggests that ARE has the potential to increase muscle mitochondrial function by activating AMPK and $PGC1{\alpha}$.

Hepatitis C Virus Non-structural Protein NS4B Can Modulate an Unfolded Protein Response

  • Zheng Yi;Gao Bo;Ye Li;Kong Lingbao;Jing Wei;Yang Xiaojun;Wu Zhenghui;Ye Linbai
    • Journal of Microbiology
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    • v.43 no.6
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    • pp.529-536
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    • 2005
  • Viral infection causes stress to the endoplasmic reticulum (ER). The response to endoplasmic reticulum stress, known as the unfolded protein response (UPR), is designed to eliminate misfolded proteins and allow the cell to recover. The role of hepatitis C virus (HCV) non-structural protein NS4B, a component of the HCV replicons that induce UPR, is incompletely understood. We demonstrate that HCV NS4B could induce activating transcription factor (ATF6) and inositol-requiring enzyme 1 (IRE1), to favor the HCV subreplicon and HCV viral replication. HCV NS4B activated the IRE1 pathway, as indicated by splicing of X box-binding protein (Xbp-1) mRNA. However, transcriptional activation of the XBP-1 target gene, EDEM (ER degradation-enhancing $\alpha-mannosidase-like$ protein, a protein degradation factor), was inhibited. These results imply that NS4B might induce UPR through ATF6 and IRE1-XBP1 pathways, but might also modify the outcome to benefit HCV or HCV subreplicon replication.

Inhibitory effects of Sargassum horneri extract against endoplasmic reticulum stress in HepG2 cells (괭생이 모자반 추출물의 소포체 스트레스 억제 효능)

  • Park, Sora;Thomas, Shalom Sara;Cha, Youn-Soo;Kim, Kyung-Ah
    • Journal of Nutrition and Health
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    • v.53 no.6
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    • pp.583-595
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    • 2020
  • Purpose: This study examined the effects of Sargassum horneri extracts on palmitic acid (PA)-induced endoplasmic reticulum (ER) stress in HepG2 cells. Methods: HepG2 cells were treated with varying concentrations of S. horneri extract or PA, and the cell viability was measured by water soluble tetrazolium salts analysis. The effective induction of ER stress and the effects of S. horneri were investigated through an examination of the ER stress-related genes, such as activating transcription factor 4 (ATF4), X-box binding protein (XBP1s), C/EBP homologous protein (CHOP), and 78-kDa glucose-regulated protein (GRP78) by quantitative reverse transcription polymerase chain reaction. The expression and activation levels of unfolded protein response (UPR) associated proteins, such as inositol-requiring enzyme-1α (IRE1α), eukaryotic translation initiation factor 2 alpha submit (eIF2α), and CHOP were examined by western blot analysis. Results: The treatment with PA increased the expression of UPR associated genes significantly and induced ER stress in a 12-hour treatment. Subsequent treatment with S. horneri reduced mRNA expression of ATF4, GRP78, and XBP1s. In addition, the protein levels of phosphate (p)-IRE1α, p-elF2α, and CHOP were also reduced by a treatment with S. horneri. An analysis of sirtuin (SIRT) mRNA expression in the S. horneri and PA-treated HepG2 cells showed that S. horneri increased the levels of SIRT2, SIRT6, and SIRT7, which indicates a possible role in reducing the expression of ER stress-related genes. Conclusion: These data indicate that S. horneri can exert an inhibitory effect on ER stress caused by PA and highlight its potential as an agent for managing various ER stress-related diseases.

Combination of Grapefruit and Rosemary Extracts Has Skin Protective Effect through MMPs, MAPKs, and the NF-κB Signaling Pathway In Vitro and In Vivo UVB-exposed Model

  • Yoon, Yeo-Cho;Choi, Hee-Jeong;Park, Ji-Hyun;Diniyah, Nurud;Shin, Hyun-A;Kim, Mi-Yeon
    • Korean Journal of Plant Resources
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    • v.32 no.6
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    • pp.633-643
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    • 2019
  • Long-term ultraviolet (UV) exposure accelerates the phenomenon of skin photo-aging by activating collagenase and elastase. In this study, we aimed to investigate the effects of a combination of grapefruit and rosemary extracts (cG&Re) on UVB-irradiated damage in HaCaT cells and dorsal mouse skin. In HaCaT cells, cG&Re recovered UVB-reduced cell viability and inhibited protein expression of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated kinases (p-Erk), c-Jun N-terminal kinases (p-JNK), and a class of MAPKs (p-P38). Also, cG&Re suppressed UVB-induced collagen and elastin degradation by decreasing matrix metalloproteinases (MMPs) and nuclear factor kappa light chain enhancer of activated B cells (NF-κB) expression, which is a transcription factor. Similar results were observed in dorsal mouse skin. Taken together, our data indicate that cG&Re prevent UVB-induced skin photo-aging due to collagen/elastin degradation via activation of MAPKs, MMPs, and the NF-κB signaling pathway in vitro and in vivo.

Antioxidant effects of fucoxanthin rich powder in rats fed with high fat diet

  • Ha, Ae Wha;Na, Se Jung;Kim, Woo Kyoung
    • Nutrition Research and Practice
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    • v.7 no.6
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    • pp.475-480
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    • 2013
  • The purpose of this study was to determine the antioxidant effect of fucoxanthin. After rats were fed a normal fat diet (NF), high fat diet (HF), and high fat with 0.2% fucoxanthin diet (HF + Fxn) for 4 weeks, the markers of oxidative stress and antioxidant capacity like lipid peroxidation, plasma total antioxidant capacity (TAC), and activities of antioxidant enzymes (catalase, superoxide dismutase (SOD), and gluthathione peroxidase (GSH-Px)) were determined. mRNA expression of transcription factor, nuclear erythroid factor like 2 (Nrf2), and its target genes such as NAD(P)H quinone oxidoreductase1 (NQO1) and heme oxygenase-1 (HO-1) were also determined. Mean weight gain in the HF + Fxn group was lower, without statistical significance, and the total food intake in the HF + Fxn group was lower than that in the HF group (P < 0.05). The activity of GSH-Px (P < 0.05) in plasma was significantly higher in the HF + Fxn group than those in the HF group (P < 0.05). In the liver, the activities of catalase (P < 0.05) and GSH-Px (P < 0.05) in the HF + Fxn group were significantly higher than those in the HF group. Plasma TAC level was significantly higher in the HF + Fxn group than that in the HF group (P < 0.05). Lipid peroxidation in plasma tended to be lower without statistical significance. Fucoxanthin supplements were shown to have higher mRNA expression of Nrf2 and NQO1 than those in the high fat diet only group (P < 0.05). In conclusion, supplementation of fucoxanthin improved the antioxidant capacity, depleted by high fat diet, by activating the Nrf2 pathway and its downstream target gene NQO1. Therefore, supplementation of fucoxanthin, especially for those who consume high fat in their diet, may benefit from reduced risk of oxidative stress.