• 제목/요약/키워드: ER${\alpha}$

검색결과 224건 처리시간 0.028초

Activation of Estrogen Receptor by Bavachin from Psoralea corylifolia

  • Park, Joon-Woo;Kim, Do-Hee;Ahn, Hye-Na;Song, Yun-Seon;Lee, Young-Joo;Ryu, Jae-Ha
    • Biomolecules & Therapeutics
    • /
    • 제20권2호
    • /
    • pp.183-188
    • /
    • 2012
  • In this study, we examined the estrogenic activity of bavachin, a component of Psoralea corylifolia that has been used as a traditional medicine in Asia. Bavachin was purified from ethanolic extract of Psoralea corylifolia and characterized its estrogenic activity by ligand binding, reporter gene activation, and endogenous estrogen receptor (ER) target gene regulation. Bavachin showed ER ligand binding activity in competitive displacement of [$^3H$] $E_2$ from recombinant ER. The estrogenic activity of bavachin was characterized in a transient transfection system using $ER{\alpha}$ or $ER{\beta}$ and estrogen-responsive luciferase plasmids in CV-1 cells with an $EC_{50}$ of 320 nM and 680 nM, respectively. Bavachin increased the mRNA levels of estrogen-responsive genes such as pS2 and PR, and decreased the protein level of $ER{\alpha}$ by proteasomal pathway. However, bavachin failed to activate the androgen receptor in CV-1 cells transiently transfected with the corresponding receptor and hormone responsive reporter plasmid. These data indicate that bavachin acts as a weak phytoestrogen by binding and activating the ER.

HepG2 세포에서 까마귀쪽나무 과육 열수 추출물의 소포체 스트레스 억제 효능 (Inhibitory Effects of Litsea japonica Flesh Water Extract against Endoplasmic Reticulum Stress in HepG2 Cells)

  • 김은옥;제갈경환;김재광;이주상;박정아;김상찬;조일제
    • 대한한의학방제학회지
    • /
    • 제26권4호
    • /
    • pp.307-318
    • /
    • 2018
  • Objectives : Endoplasmic reticulum (ER) stress designates cellular responses to the accumulation of misfolded and unfolded proteins in ER, which is related to a variety of liver diseases. Present study investigated the inhibitory effects of Litsea japonica flesh water extract (LJE) aganist ER stress. Methods : After HepG2 cells were pretreated with LJE and subsequently exposed to tunicamycin (Tm) or thapsigargin (Tg), expression of C/EBP homologous protein (CHOP), glucose regulated protein 78 kDa (GRP78), asparagine synthetase (ASNS), and endoplasmic reticulum DnaJ homologue 4 (ERDJ4) were determined by immunoblot and real-time PCR analysis. Three canonical signaling pathways in response to ER stress were examined to explore molecular mechanisms involved. Results : Pretreatment of 1 mg/mL LJE inhibited Tm- or Tg-induced CHOP expression, while L. japonica fruit water extract did not. In addition, LJE decreased the levels of GRP78, ASNS, and ERDJ4 mRNA by Tm. Moreover, phosphorylations of eukaryotic translation initiation factor $2{\alpha}$ and inositol-requiring enzyme 1, expression of nuclear form of activating transcription factor $6{\alpha}$, and transactivation of ER stress response element- and unfolded protein response element-harboring luciferase activities were inhibited by LJE pretreatment. Conclusions : Present results suggest that LJE would be a candidate to prevent or treat ER stress-mediated liver injuries.

Er:YAG 레이저와 Er,Cr: YSGG 레이저가 염증유발 마우스조직에 미치는 영향 (The Effect of ER:YAG Laser & ER,CR:YSGG Laser on the Tissue of the Inflammation-Induced Mouse)

  • 박태일;이형석;이희종;채창훈;이영주;변광섭;홍순민;최미라;박준우
    • Maxillofacial Plastic and Reconstructive Surgery
    • /
    • 제32권5호
    • /
    • pp.396-405
    • /
    • 2010
  • Purpose: This study was performed to find out the effects of the Er:YAG laser (Key Laser) & Er,Cr:YSGG laser (Water Laser) on inflammatory tissues. Materials and Methods: It was performed on about 20 g, 6 weeks male ICR mouses. They were grouped into the control (negative), the inflammation induced 'control'(positive), Er,Cr:YSGG laser exposured group after inducing inflammation, Er:YAG lasere exposured group after inducing inflammation each 15 mouses. The mouses were applicated 0.5% DNFB 1 cc on ear skin twice a day for 4 days until symptom expression. After laser exposure, ear tissues were extracted and defined gene expression by RT-PCR. Then, tissue staining, lymphocytes observation, electromicroscophic laboratory were carried out. Results: Interleukin-$1{\beta}$ was expressed much less in the A-laser exposed group. Interleukin-$1{\beta}$ & Tumor Necrosis Factor-${\alpha}$ were expressed 7 times lesser in the A-laser exposed group. The number of Lymphocytes related to inflammation was decreased rapidly in the A-laser exposed group in vivo. he number of cavity recovered normal was a little bigger in the A-laser exposed group after 5 days Conclusion: The expression of IL-$1{\beta}$ & TNF-${\alpha}$, hitologic change, observation with electron microscope shows that Erbium laser exposure causes lesser inflammation with A-laser rather than B-laser.

Effects of Red Ginseng-Ejung-tang Water Extract on Cytokine Production in LPS-induced Mouse Macrophages

  • Park, Wansu
    • 대한한의학회지
    • /
    • 제33권4호
    • /
    • pp.42-49
    • /
    • 2012
  • Objectives: The purpose of this study was to investigate effects of Red Ginseng-Ejung-tang Water Extract (ER) on cytokine production in RAW 264.7 mouse macrophages stimulated by lipopolysaccharide (LPS). Methods: Levels of various cytokines such as interleukin (IL)-6, IL-10, IL-2, IL-12p70, vascular endothelial growth factor (VEGF), monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protein (MIP)-2, keratinocyte-derived chemokine (KC), tumor necrosis factor (TNF)-alpha, granulocyte macrophage colony-stimulating factor (GM-CSF) were measured by high-throughput multiplex bead array cytokine assay based on xMAP (multi-analyte profiling beads) technology. Results: ER significantly decreased levels of IL-6, IL-10, IL-2, IL-12p70, VEGF, and MCP-1 for 24 hrs incubation at the concentrations of 25, 50, and $100{\mu}g/mL$ in LPS-induced RAW 264.7 cells (P < 0.05). But ER did not exert significant effects on production of MIP-2, KC, TNF-${\alpha}$, and GM-CSF in LPS-induced RAW 264.7 cells. Conclusions: These results suggest that ER has an anti-inflammatory property related with its inhibition of cytokine production in LPS-induced macrophages.

Estrogen activity of Silkworm (Bombyx mori) Pupa water extract and its fractions

  • Ryu, Jae-Sung;Jo, Gyeong-Jong;Jin, Jung-Woo;Yang, Hyo-Jung;Park, Yong-Il;Na, Ye-Seul;Nam, Kyung-Su;Keum, Kyung-Soo;Choo, Young-Kug
    • Advances in Traditional Medicine
    • /
    • 제8권3호
    • /
    • pp.228-235
    • /
    • 2008
  • This study was conducted to evaluate the estrogen activity of silkworm (Bombyx mori) pupa extracts and their fractions. Powdered samples of freeze-dried silkworm pupa were extracted at room temperature (RT), $40^{\circ}C$, $60^{\circ}C$, $80^{\circ}C$, and $100^{\circ}C$ in water (D.W), chloroform, ethyl acetate, and methanol for 6h and then filtered (0.45 um). The extracts were then freeze-dried. The estrogenic activity of these extracts was then investigated by competition binding assays using estrogen receptor ${\alpha}\;(ER{\alpha})$ and $ER{\beta}$, and by evaluating their effects on the proliferation of the human breast cancer cell line, MCF-7. Among the extracts evaluated, water extracts prepared at RT showed the highest binding affinity to $ER{\alpha}$ ($IC_{50}$, 1.76 ug/ml) and $ER{\beta}$ ($IC_{50}$, 0.07 ug/ml). In addition, MCF-7 cells that were treated with 62.5 ug/ml of the RT extract showed the greatest increase in proliferation (2-fold; 1291.79%) when compared to control cells (659.82%). Next, the water extract that was prepared at RT (sample 1) was dissolved in D.W. and further fractionated using a Dowex 50W - 8X ($H^+$) column. The flow-through and wash were then pooled together and freeze-dried (sample 2). The bound materials were then eluted with 20 mM NaCl, after which they were applied to a Dowex 1X2 - 200 ($Cl^-$) column and washed with D.W. to remove the sodium ions. The eluants were then freeze-dried (sample 3). Of these fractions, sample 2 showed the highest binding affinity to ER{\alpha} ($IC_{50}$, 1.44 ug/ml) and $ER{\beta}$ ($IC_{50}$, 1.18 ug/ml). In addition, MCF-7 cells that were treated with sample 2 (15.6 ug/ml) showed the largest increase in growth (1159.39%) when compared to control cells (525.26%). Taken together, these results suggest that the fraction of the RT water extract of silkworm pupa referred to as sample 2 may be useful as a phytoestrogen.

광전 소자용 $CdGaInS_4:Er^{3+}$ 단결정의 광학적 에너지 갭의 온도의존성 (Temperature Dependence of Optical Energy Gaps of $CdGaInS_4:Er^{3+}$ Single Crystals for Optoelectronic device)

  • 김형곤;김병철;방태환;현승철;김덕태;손경춘
    • 대한전기학회:학술대회논문집
    • /
    • 대한전기학회 2000년도 학술대회 논문집 전문대학교육위원
    • /
    • pp.56-59
    • /
    • 2000
  • $CdGaInS_4$ and $CdGaInS_4:Er^{3+}$ single crystals crystallized in the rhombohedral(hexagonal) structure. with lattice constants $a=3.913{\AA},\;c=37.245{\AA}$ for $CdGaInS_4$, and $a=3.899{\AA}$ and $c=36.970{\AA}$ for $CdGaInS_4:Er^{3+}$. The optical absorption measured near the fundamental band edge showed that the optical energy band structure of these compounds had a direct and indirect band gap. the direct and indirect energy gaps are found to be 2.771 and 2.503 eV for $CdGaInS_4$, and 2.665 and 2.479 eV for $CdGaInS_4:Er^{3+}$ at 10 K. The temperature dependence of the optical energy gap was well represented by the Varshni equation. In $CdGaInS_4$, the values of ${\alpha},\;{\beta}$ of the direct and the indirect energy gap were found to be $7.57{\times}10^{-4}eV/K$. $6.53{\times}10^{-4}eV/K$ and 240K. 197K. and the values of ${\alpha}$ and ${\beta}$ of the direct and the indirect energy gap in the $CdGaInS_4:Er^{3+}$ were given by $8.28{\times}10^{-4}eV/K,\;2.08{\times}10^{-4}eV/K$ and 425 K, 283 K, respectively.

  • PDF

Anti-inflammatory effect of Lycium barbarum on polarized human intestinal epithelial cells

  • Lee, So-Rok;Hwang, Hye-Jeong;Yoon, Ju-Gyeong;Bae, Eu-Young;Goo, Kyo-Suk;Cho, Sang-Joon;Cho, Jin Ah
    • Nutrition Research and Practice
    • /
    • 제13권2호
    • /
    • pp.95-104
    • /
    • 2019
  • BACKGROUND/OBJECTIVES: Inflammatory Bowel Disease (IBD) has rapidly escalated in Asia (including Korea) due to increasing westernized diet patterns subsequent to industrialization. Factors associated with endoplasmic reticulum (ER) stress are demonstrated to be one of the major causes of IBD. This study was conducted to investigate the effect of Lycium barbarum (L. barbarum) on ER stress. MATERIALS/METHODS: Mouse embryonic fibroblast (MEF) cell line and polarized Caco-2 human intestinal epithelial cells were treated with crude extract of the L. chinense fruit (LF). Paracellular permeability was measured to examine the effect of tight junction (TJ) integrity. The regulatory pathways of ER stress were evaluated in MEF knockout (KO) cell lines by qPCR for interleukin (IL) 6, IL8 and XBP1 spliced form (XBP1s). Immunoglobulin binding protein (BiP), XBP1s and CCAAT/enhancer-binding homologous protein (CHOP) expressions were measured by RT-PCR. Scanning Ion Conductance Microscopy (SICM) at high resolution was applied to observe morphological changes after treatments. RESULTS: Exposure to LF extract strengthened the TJ, both in the presence and absence of inflammation. In polarized Caco-2 pretreated with LF, induction in the expression of proinflammatory marker IL8 was not significant, whereas ER stress marker XBP1s expression was significantly increased. In wild type (wt) MEF cells, IL6, CHOP and XBP1 spliced form were dose-dependently induced when exposed to $12.5-50{\mu}g/mL$ extract. However, absence of XBP1 or $IRE1{\alpha}$ in MEF cells abolished this effect. CONCLUSION: Results of this study show that LF treatment enhances the barrier function and reduces inflammation and ER stress in an $IRE1{\alpha}$-XBP1-dependent manner. These results suggest the preventive effect of LF on healthy intestine, and the possibility of reducing the degree of inflammatory symptoms in IBD patients.

Ginsenoside Rg1 activates ligand-independent estrogenic effects via rapid estrogen receptor signaling pathway

  • Gao, Quan-Gui;Zhou, Li-Ping;Lee, Vien Hoi-Yi;Chan, Hoi-Yi;Man, Cornelia Wing-Yin;Wong, Man-Sau
    • Journal of Ginseng Research
    • /
    • 제43권4호
    • /
    • pp.527-538
    • /
    • 2019
  • Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

비수리(Lespedeza cuneata G. Don) 메탄올 추출물로부터 분획된 용매분획물의 항산화활성과 α-Glucosidase 저해활성 (Antioxidant and α-Glucosidase Inhibition Activities of Solvent Fractions from Methanolic Extract of Sericea Lespedeza (Lespedeza cuneata G. Don))

  • 김현영;고지연;송석보;김정인;서혜인;이재생;곽도연;정태욱;김기영;오인석;정헌상;우관식
    • 한국식품영양과학회지
    • /
    • 제41권11호
    • /
    • pp.1508-1514
    • /
    • 2012
  • 비수리의 식품학적 이용가능성을 확인해 보고자 항산화성분 및 항산화활성, superoxide dismutase 유사활성, ${\alpha}$-glucosidase 저해활성 등에 대해 검토하였다. 비수리 메탄올 추출물과 hexane, chloroform, ethyl acetate, butanol 및 물 분획 등 순차적 용매분획물의 총 폴리페놀 함량은 각각 12.44, 3.61, 6.39, 27.11, 20.00 및 9.32 mg GAE/g extract residue(ER)로 나타났으며, 총 플라보노이드 함량은 각각 2.94, 9.92, 7.77, 9.27, 5.11 및 2.66 mg CE/g ER, 총 탄닌 함량은 각각 8.75, 10.04, 7.42, 17.32, 11.65 및 7.61 mg TAE/g ER, 총 프로안토시아니딘의 함량은 346.09, 63.50, 103.76, 288.62, 231.99 및 $358.48{\mu}g$ CE/g ER로 나타났다. 비수리 메탄올 추출물과 hexane, chloroform, ethyl acetate, butanol 및 물 분획물의 DPPH radical 소거활성은 각각 20.62, 5.16, 9.29, 20.80, 20.00 및 20.79 mg TE/g ER, ABTS radical 소거활성은 각각 33.86, 9.24, 17.36, 33.76, 33.49 및 33.86 mg TE/g ER로 나타났다. SOD 유사활성은 각각 4.12, 0.61, 2.01, 9.89, 13.47 및 11.82 unit/mL의 활성을 보여 butanol 분획과 물 분획에서 유의적으로 높은 활성을 나타내었고 ${\alpha}$-glucosidase 저해활성은 물 분획 50 및 $25{\mu}g/mL$에서 각각 93.85 및 61.64%로 높은 저해활성을 보이는 것으로 나타났다. 이상의 결과에서 비수리 추출물은 항산화성분 및 항산화활성, SOD 유사활성, ${\alpha}$-glucosidase 저해활성을 가지는 물질을 함유한 것으로 보이며, 체내 및 식품에서 활성산소 종 제거에 도움을 줄 수 있을 것으로 보인다.

Emodin Inhibits Breast Cancer Cell Proliferation through the ERα-MAPK/Akt-Cyclin D1/Bcl-2 Signaling Pathway

  • Sui, Jia-Qi;Xie, Kun-Peng;Zou, Wei;Xie, Ming-Jie
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제15권15호
    • /
    • pp.6247-6251
    • /
    • 2014
  • Background: The aim of the present study was to investigate the involvement of emodin on the growth of human breast cancer MCF-7 and MDA-MB-231 cells and the estrogen (E2) signal pathway in vitro. Materials and Methods: MTT assays were used to detect the effects of emodin on E2 induced proliferation of MCF-7 and MDA-MB-231 cells. Flow cytometry (FCM) was applied to determine the effect of emodin on E2-induced apoptosis of MCF-7 cells. Western blotting allowed detection of the effects of emodin on the expression of estrogen receptor ${\alpha}$, cyclin D1 and B-cell lymphoma-2 (Bcl-2), mitogen-activated protein kinases (MAPK) and phosphatidylinostiol 3-kinases (PI3K). Luciferase assays were emplyed to assess transcriptional activity of $ER{\alpha}$. Results: Emodin could inhibit E2-induced MCF-7 cell proliferation and anti-apoptosis effects, and arrest the cell cycle in G0/G1 phase, further blocking the effect of E2 on expression and transcriptional activity of $ER{\alpha}$. Moreover, Emodin influenced the ER ${\alpha}$ genomic pathway via downregulation of cyclin D1 and Bcl-2 protein expression, and influenced the non-genomic pathway via decreased PI3K/Akt protein expression. Conclusions: These findings indicate that emodin exerts inhibitory effects on MCF-7 cell proliferation via inhibiting both non-genomic and genomic pathways.