• 제목/요약/키워드: ER-${\alpha}$

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Effect of Exercise Intensity on Unfolded Protein Response in Skeletal Muscle of Rat

  • Kim, Kihoon;Kim, Yun-Hye;Lee, Sung-Hye;Jeon, Man-Joong;Park, So-Young;Doh, Kyung-Oh
    • The Korean Journal of Physiology and Pharmacology
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    • 제18권3호
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    • pp.211-216
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    • 2014
  • Endoplasmic reticulum (ER) stress, unfolded protein response (UPR), and mitochondrial biogenesis were assessed following varying intensities of exercise training. The animals were randomly assigned to receive either low- (LIT, n=7) or high intensity training (HIT, n=7), or were assigned to a control group (n=7). Over 5 weeks, the animals in the LIT were exercised on a treadmill with a $10^{\circ}$ incline for 60 min at a speed of 20 m/min group, and in the HIT group at a speed of 34 m/min for 5 days a week. No statistically significant differences were found in the body weight, plasma triglyceride, and total cholesterol levels across the three groups, but fasting glucose and insulin levels were significantly lower in the exercise-trained groups. Additionally, no statistically significant differences were observed in the levels of PERK phosphorylation in skeletal muscles between the three groups. However, compared to the control and LIT groups, the level of BiP was lower in the HIT group. Compared to the control group, the levels of ATF4 in skeletal muscles and CHOP were significantly lower in the HIT group. The HIT group also showed increased PGC-$1{\alpha}$ mRNA expression in comparison with the control group. Furthermore, both of the trained groups showed higher levels of mitochondrial UCP3 than the control group. In summary, we found that a 5-week high-intensity exercise training routine resulted in increased mitochondrial biogenesis and decreased ER stress and apoptotic signaling in the skeletal muscle tissue of rats.

ARYL HYDROCARBON- AND ESTROGEN-MEDIATED SIGNALS POSSIBLY CROSS TALK TO REGULATE CYP1A1 GENE EXPRESSION

  • Joung, Ki-Eun;Kim, Yeo-Woon;Min, Kyung-Nan;Sheen, Yhun-Yhong
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 한국응용약물학회 2001년도 추계학술대회 및 정기총회
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    • pp.112-112
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    • 2001
  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways by enhancing ligand metabolism, altering hormone synthesis, down regulating receptor levels, and interfering with gene transcription. And TCDD-mediated gene transactivation via the AhR has been shown to be dependent upon estrogen receptor (ER) expression in human breast cancer cells. In the present study, we have examined the effect of natural estrogen, phytoestrognes and environmental estrogens on the regulation of CYP1A1 gene expression in MCF-7 human breast cancer cell line. that ER and AhR are co-expressed. pCYP1A1 -luc reporter gene was transiently transfected into MCF-7 cells. These cells were treated with various chemicals and then luciferase assay was carried out. 17be1a-estradiol significantly inhibited TCDD stimulated luciferase activity dose dependently and this inhibition was partially recovered by concomitant treatment of tamoxifen. 17beta-estradiol metabolites, 2-hydroxyestradiol and 16alpha-estriol resulted in less potent inhibitory effect than estradiol and synthetic estrogen, diethylstilbestrol (DES) showed no effect on CYP1A1 gene expression. This study demonstrated that estrogen down-regulated TCDD stimulated CYP1A1 expression via ER mediation. And we have found out that several flavonoids such as genistein, kaempferol, daidzein, naringenin, and alkylphenols such as nonylphenol, 4-octylphenol and resveratrol also inhibited TCDD induced CYP1A1 expression like estrogen.

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Identification of Genes Differentially Expressed in the MCF-7 Cells Treated with Mitogenic Estrogens

  • Cheon, Myeong-Sook;Yoon, Tae-Sook;Lee, Do-Yeon;Choi, Go-Ya;Lee, A-Yeong;Choo, Byung-Kil;Kim, Ho-Kyoung
    • Journal of Applied Biological Chemistry
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    • 제51권1호
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    • pp.1-6
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    • 2008
  • Estrogens, a group of steroid compounds functioning as the primary female sex hormone, play an important role in the development and progression of breast cancer. In this study, using a novel annealing control primer-based GeneFishing PCR technology, five differentially expressed genes (DEGs), expressed using 10nM mitogenic estrogens, $17{\beta}$-estradiol (E2) and $16{\alpha}$-hydroxyestrone ($16{\alpha}$-OHE1), were selected from the estrogen receptor (ER)-positive MCF-7 human breast cancer cells. The DEGs, MRPL42, TUBA1B, SSBP1, KNCT2, and RUVBL1, were identified by comparison with the known genes via direct sequencing and sequence homology search in BLAST. Quantitative real-time PCR data showed that two DEGs, tubulin ${\alpha}1b$ and kinetochore associated 2, were greater than 2-fold upregulated by E2 or $16{\alpha}$-OHE1. Both genes could be new biomarkers for the treatment and prognosis of cancers, and further study may provide insights into the molecular mechanisms underlying development and progression of breast cancer.

Anti-Oxidative and Anti-Proliferative Effect of 70% Ethanol Extracts from Green Pepper (Capsicum annuum L. cv. DangZo) (당조고추 70% 에탄올추출물의 항산화 및 항암활성측정)

  • Lee, Youn Ri
    • The Korean Journal of Food And Nutrition
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    • 제30권5호
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    • pp.1127-1131
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    • 2017
  • To evaluate the anti-oxidant and anti-tumor potential of the green pepper (Capsicum annuum L. cv. DangZo), total polyphenol content, radical scavenging activities and anti-tumor properties were measured. The total polyphenol content of the 70% ethanol extracts from green pepper (Capsicum annuum L. cv. DangZo) was 30.29 mg gallic acid equivalent/g extract. The DPPH radical and hydroxyl radical scavenging activities of 70% ethanol extracts of green pepper (Capsicum annuum L. cv. DangZo) were documented at 2.87 and 10.55, respectively. For ${\alpha}$-glucosidase and ${\alpha}$-amylase inhibitory activity, 70% ethanol extracts of green pepper (Capsicum annuum L. cv. DangZo) were documented at 35.67% and 58.41% respectively. The green pepper (Capsicum annuum L. cv. DangZo) demonstrated greater capability in terms of anti-neoplastic activity vis-a-vis colon cancer cell lines when compared to other cancer cell lines.s. er (Capsicum annuum L. cv. DangZo) higher activities of anticancer activities on colon cancer cell lines compared to other cancer cell lines.

Gene Expression Pattern during Early Embryogenesis and Transcriptional Activities of Estrogen Receptor-Related Receptor(ERR) in Sea Urchin, Strongylocentrotus nudus (둥근성게(Strongylocentrotus nudus) Estrogen Receptor-Related Receptor(ERR)의 초기 발생시 유전자 발현 패턴과 전사 활성)

  • Maeng, Se-Jung;Kim, Mi-Soon;Sohn, Young-Chang
    • Development and Reproduction
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    • 제13권4호
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    • pp.249-256
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    • 2009
  • The estrogen receptor-related receptors (ERRs) are a group of nuclear receptor superfamily of transcription factors. ERRs and estrogen receptors (ERs) have overlapping affinities for coactivators and DNA binding sites, but differ markedly in ligand binding and activation. The three mammalian ERR genes have been implicated in diverse physiological processes ranging from placental development to maintenance of bone density, whereas the molecular diversity, function, and regulation of ERRs in non-mammalian species are not well understood. In the present study, to investigate the involvement of ERR in transcription and embryogenesis in marine invertebrates, a cDNA encoding ERR (SnERR) was cloned from the gonad in Strongylocentrotus nudus, by polymerase chain reaction (PCR). The amino acid sequence of SnERR showed high homology with that of S. purpuratus (91%). A phylogenetic tree clearly showed that SnERR is a member of the ERR family and clustered in echinodermata group as supported by a high bootstrap value. We examined gene expression of SnERR during embryonic development of S. nudus using real-time PCR. During the embryonic development, the mRNA of ERR was significantly high levels in early development stages (4~64 cell) and larval stages. The SnERR slightly activated transcription through the classical estrogen response elements (EREs) in the presence of genistein. In addition, peroxisome proliferator-activated receptor $\gamma$ coactivator (PGC)-$1\alpha$ knwon as a coactivator of ERR enhanced the snERR-mediated transactivation, suggesting that the PGC-$1\alpha$ is a coactivator of SnERR.

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Sericin Enhances Secretion of Thyroglobulin in the Thyrocytes (갑상선세포에서 sericin에 의한 thyroglobulin의 분비증가)

  • Jin, Cho-Yi;Song, Seong-Hee;Go, Young-Hwa;Kwon, Ki-Sang;Yun, Eun-Young;Goo, Tae-Won;Yeo, Joo-Hong;Kim, Seung-Whan;Choi, Jong-Soon;Yu, Kweon;Kwon, O-Yu
    • Journal of Life Science
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    • 제20권8호
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    • pp.1249-1253
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    • 2010
  • Sericin is a type of high molecular weight water-soluble glycoprotein surrounding fibroin (silk protein) that has been used as a cell culture supplement and accelerates cell proliferation in various serum-free media. The purpose of this study was to investigate the enhancing effect of thyroglobulin (Tg) secretion by sericin in thyrocytes, FRTL-5 cells. While Tg-mRNA expression was not enhanced, a secreted form of Tg was obviously increased by sericin. In this status, expression of both endoplasmic reticulum (ER) molecular chaperones (Bip & calreticulin) and ER membrane proteins (IRE1, PERK & ATF6) was enhanced. The proximal step of IRE1, XBP1 mRNA splicing was slightly detected however, the proximal step of PERK, phosphorylation of $eIF2{\alpha}$, was changeless. In addition, sericin enhanced cell viability by the MTT assay. The above results showing the ability of sericin to promote protein production demonstrated its potential usefulness as a new biomaterial.

Cell Growth of BG-1 Ovarian Cancer Cells was Promoted by 4-Tert-octylphenol and 4-Nonylphenol via Downregulation of TGF-β Receptor 2 and Upregulation of c-myc

  • Park, Min-Ah;Hwang, Kyung-A;Lee, Hye-Rim;Yi, Bo-Rim;Choi, Kyung-Chul
    • Toxicological Research
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    • 제27권4호
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    • pp.253-259
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    • 2011
  • Transforming growth factor ${\beta}$ (TGF-${\beta}$) is involved in cellular processes including growth, differentiation, apoptosis, migration, and homeostasis. Generally, TGF-${\beta}$ is the inhibitor of cell cycle progression and plays a role in enhancing the antagonistic effects of many growth factors. Unlike the antiproliferative effect of TGF-${\beta}$, E2, an endogeneous estrogen, is stimulating cell proliferation in the estrogen-dependent organs, which are mediated via the estrogen receptors, $ER{\alpha}$ and $ER{\beta}$, and may be considered as a critical risk factor in tumorigenesis of hormone-responsive cancers. Previous researches reported the cross-talk between estrogen/$ER{\alpha}$ and TGF-${\beta}$ pathway. Especially, based on the E2-mediated inhibition of TGF-${\beta}$ signaling, we examined the inhibition effect of 4-tert-octylphenol (OP) and 4-nonylphenol (NP), which are well known xenoestrogens in endocrine disrupting chemicals (EDCs), on TGF-${\beta}$ signaling via semi-quantitative reverse-transcription PCR. The treatment of E2, OP, or NP resulted in the downregulation of TGF-${\beta}$ receptor2 (TGF-${\beta}$ R2) in TGF-${\beta}$ signaling pathway. However, the expression level of TGF-${\beta}1$ and TGF-${\beta}$ receptor1 (TGF-${\beta}$ R1) genes was not altered. On the other hand, E2, OP, or NP upregulated the expression of a cell-cycle regulating gene, c-myc, which is a oncogene and a downstream target gene of TGF-${\beta}$ signaling pathway. As a result of downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc, E2, OP, or NP increased cell proliferation of BG-1 ovarian cancer cells. Taken together, these results suggest that E2 and these two EDCs may mediate cancer cell proliferation by inhibiting TGF-${\beta}$ signaling via the downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc oncogene. In addition, it can be inferred that these EDCs have the possibility of tumorigenesis in estrogen-responsive organs by certainly representing estrogenic effect in inhibiting TGF-${\beta}$ signaling.

Lethal (2) Essential for Life [l(2)efl] Gene in the Two-spotted Cricket, Gryllus bimaculatus (Orthoptera: Gryllidae) (쌍별귀뚜라미(Gryllus bimaculatus)의 l(2)efl cDNA 클로닝과 발현분석)

  • Kwon, Kisang;Lee, Nuri;Kwon, O-Yu
    • Journal of Life Science
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    • 제31권7호
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    • pp.671-676
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    • 2021
  • A cDNA encoding the protein lethal (2) essential for life [l(2)efl] was cloned from Gryllus bimaculatus and named GBl(2)efl. This protein is composed of 189 amino acids, including an N-glycosylation site and 15 phosphorylation sites. Its predicted molecular mass is 21.19 kDa, with a theoretical isoelectric point of 6.2. The secondary structure of GBl(2)efl was predicted from the identification of random coils (56.08%), alpha helices (22.22%), extended strands (17.99%), and beta turns (3.7%) through sequence analyses. A homology analysis revealed that GBl(2)efl exhibited a high similarity with other species at the amino acid level, ranging from 52% to 69%. While GBl(2)efl mRNA expression was higher in the dorsal longitudinal flight muscle following a three-day starvation and in the Malpighian tubules following a one-day starvation, no changes in expression were detected in other tissues. Furthermore, tunicamycin-induced endoplasmic reticulum (ER) stress resulted in an approximately 1.8-fold higher expression in the fat body compared with the wild type.

Functional Characterization and Application of the HpOCH2 Gene, Encoding an Initiating $\alpha$l,6-Mannosyltransferase, for N-glycan Engineering in the Methylotrophic Yeast Hansenula polymorpha

  • Kim, Moo-Woong;Kim, Eun-Jung;Kim, Jeong-Yoon;Rhee, Sang-Ki;Kang, Hyun-Ah
    • Proceedings of the Korean Society for Applied Microbiology Conference
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    • 한국미생물생명공학회 2004년도 Annual Meeting BioExibition International Symposium
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    • pp.278-281
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    • 2004
  • The $\alpha$1,6-mannosyltransferase encoded by Saccharomyces cerevisiae OCH1 plays a key role for the outer chain initiation of the N-linked oligosaccharides. A search for Hansenula polymorpha genes homologous to S. cerevisiae OCHI (ScOCH1) has revealed seven open reading frames (ORF100, ORF142, ORF168, ORF288, ORF379, ORF576, ORF580). All of the seven ORFs are predicted to be a type II integral membrane protein containing a transmembrane domain near the amino-terminal region and has a DXD motif, which has been found in the active site of many glycosyltransferases. Among this seven-membered OCH1 gene family of H. polymorpha, we have carried out a functional analysis of H. polymorpha ORF168 (HpOCH2) showing the highest identity to ScOCH1. Inactivation of this protein by disruption of corresponding gene resulted in several phenotypes suggestive of cell wall defects, including hypersensitivity to hygromycin B and sodium deoxycholate. The structural analysis of N-glycans synthesized in HpOCH2-disrupted strain (Hpoch2Δ) and the in vitro $\alpha$1,6-mannosyltransferase activity assay strongly indicate that HpOch2p is a key enzyme adding the first $\alpha$1,6-mannose residue on the core glycan Man$_{8}$GlcNAc$_2$. The Hpoch2Δ was further genetically engineered to synthesize a recombinant glycoprotein with the human compatible N-linked oligosaccharide, Man$_{5}$GlcNAc$_2$, by overexpression of the Aspergillus saitoi $\alpha$1,2-mannosidase with the 'HDEL” ER retention signal.gnal.

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Effects of laser-irradiated dentin on shear bond strength of composite resin (레이저 처리가 상아질과 복합 레진의 결합에 미치는 영향)

  • Kim, Sung-Sook;Park, Jong-Il;Lee, Jae-In;Kim, Gye-Sun;Cho, Hye-Won
    • The Journal of Korean Academy of Prosthodontics
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    • 제46권5호
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    • pp.520-527
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    • 2008
  • Purpose: This study was conducted to evaluate the shear bond strength of composite resin to dentin when etched with laser instead of phosphoric acid. Material and methods: Recently extracted forty molars, completely free of dental caries, were embedded into acrylic resin. After exposing dentin with diamond saw, teeth surface were polished with a series of SiC paper. The teeth were divided into four groups composed of 10 specimens each; 1) no surface treated group as a control 2) acid-etched with 35%-phosphoric acid 3) Er:YAG laser treated 4) Er,Cr:YSGG laser treated. A dentin bonding agent (Adapter Single Bond2, 3M/ESPE) was applied to the specimens and then transparent plastic tubes (3 mm of height and diameter) were placed on each dentin. The composite resin was inserted into the tubes and cured. All the specimens were stored in distilled water at $37^{\circ}C$ for 24 hours and the shear bond strength was measured using a universal testing machine (Z020, Zwick, Germany). The data of tensile bond strength were statistically analyzed by one-way ANOVA and Duncan's test at ${\alpha}$= 0.05. Results: The bond strengths of Er:YAG laser-treated group was $3.98{\pm}0.88$ MPa and Er,Cr:YSGG laser-treated group showed $3.70{\pm}1.55$ MPa. There were no significant differences between two laser groups. The control group showed the lowest bond strength, $1.52{\pm}0.42$ MPa and the highest shear bond strength was presented in acid-etched group, $7.10{\pm}1.86$ MPa (P < .05). Conclusion: Laser-etched group exhibited significantly higer bond strength than that of control group, while still weaker than that of the phosphoric acid-etched group.