• 제목/요약/키워드: ER${\alpha}$

검색결과 224건 처리시간 0.026초

Inhibition of ER Stress by 2-Aminopurine Treatment Modulates Cardiomyopathy in a Murine Chronic Chagas Disease Model

  • Ayyappan, Janeesh Plakkal;lizardo, Kezia;Wang, Sean;Yurkow, Edward;Nagajyothi, Jyothi F
    • Biomolecules & Therapeutics
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    • 제27권4호
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    • pp.386-394
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    • 2019
  • Trypanosoma cruzi infection results in debilitating cardiomyopathy, which is a major cause of mortality and morbidity in the endemic regions of Chagas disease (CD). The pathogenesis of Chagasic cardiomyopathy (CCM) has been intensely studied as a chronic inflammatory disease until recent observations reporting the role of cardio-metabolic dysfunctions. In particular, we demonstrated accumulation of lipid droplets and impaired cardiac lipid metabolism in the hearts of cardiomyopathic mice and patients, and their association with impaired mitochondrial functions and endoplasmic reticulum (ER) stress in CD mice. In the present study, we examined whether treating infected mice with an ER stress inhibitor can modify the pathogenesis of cardiomyopathy during chronic stages of infection. T. cruzi infected mice were treated with an ER stress inhibitor 2-Aminopurine (2AP) during the indeterminate stage and evaluated for cardiac pathophysiology during the subsequent chronic stage. Our study demonstrates that inhibition of ER stress improves cardiac pathology caused by T. cruzi infection by reducing ER stress and downstream signaling of phosphorylated eukaryotic initiation factor ($P-elF2{\alpha}$) in the hearts of chronically infected mice. Importantly, cardiac ultrasound imaging showed amelioration of ventricular enlargement, suggesting that inhibition of ER stress may be a valuable strategy to combat the progression of cardiomyopathy in Chagas patients.

Inhibition of endoplasmic reticulum stress in high-fat-diet-induced obese C57BL/6 mice: Efficacy of a novel extract from mulberry (Morus alba) leaves fermented with Cordyceps militaris

  • Lee, Mi Rim;Bae, Su Ji;Kim, Ji Eun;Song, Bo Ram;Choi, Jun Young;Park, Jin Ju;Park, Ji Won;Kang, Mi Ju;Choi, Hyeon Jun;Choi, Young Whan;Kim, Kyung Mi;Hwang, Dae Youn
    • Laboraroty Animal Research
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    • 제34권4호
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    • pp.288-294
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    • 2018
  • A few clues about correlation between endoplasmic reticulum (ER) stress and mulberry (Morus alba) leaves were investigated in only the experimental autoimmune myocarditis and streptozotocin-induced diabetes. To investigate whether a novel extract of mulberry leaves fermented with Cordyceps militaris (EMfC) could suppress ER in fatty liver, alterations in the key parameters for ER stress response were measured in high fat diet (HFD)-induced obese C57L/6 mice treated with EMfC for 12 weeks. The area of adipocytes in the liver section were significantly decreased in the HFD+EMfC treated group as compared to the HFD+Vehicle treated group, while their level was higher in HFD+Vehicle treated group than No treated group. The level of the eukaryotic initiation factor 2 alpha ($eIF2{\alpha}$) and inositol-requiring enzyme 1 beta ($IRE1{\alpha}$) phosphorylation and CCAAT-enhancer-binding protein homologous protein (CHOP) expression were remarkably enhanced in the HFD+Vehicle treated group. However, their levels were restored in the HFD+EMfC treated group, although some differences were detected in the decrease rate. Similar recovery was observed on the ER stress-induced apoptosis. The level of Caspase-3, Bcl-2 and Bax were decreased in the HFD+EMfC and HFD+orlistat (OT) treated group compared to the HFD+Vehicle treated group. The results of the present study therefore provide first evidence that EMfC with the anti-obesity effects can be suppressed ER stress and ER stress-induced apoptosis in the hepatic steatosis of HFD-induced obesity model.

Tectoridin, a Poor Ligand of Estrogen Receptor α, Exerts Its Estrogenic Effects via an ERK-Dependent Pathway

  • Kang, Kyungsu;Lee, Saet Byoul;Jung, Sang Hoon;Cha, Kwang Hyun;Park, Woo Dong;Sohn, Young Chang;Nho, Chu Won
    • Molecules and Cells
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    • 제27권3호
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    • pp.351-357
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    • 2009
  • Phytoestrogens are the natural compounds isolated from plants, which are structurally similar to animal estrogen, $17{\beta}$-estradiol. Tectoridin, a major isoflavone isolated from the rhizome of Belamcanda chinensis. Tectoridin is known as a phytoestrogen, however, the molecular mechanisms underlying its estrogenic effect are remained unclear. In this study we investigated the estrogenic signaling triggered by tectoridin as compared to a famous phytoestrogen, genistein in MCF-7 human breast cancer cells. Tectoridin scarcely binds to ER ${\alpha}$ as compared to $17{\beta}$-estradiol and genistein. Despite poor binding to ER ${\alpha}$, tectoridin induced potent estrogenic effects, namely recovery of the population of cells in the S-phase after serum starvation, transactivation of the estrogen response element, and induction of MCF-7 cell proliferation. The tectoridin-induced estrogenic effect was severely abrogated by treatment with U0126, a specific MEK1/2 inhibitor. Tectoridin promoted phosphorylation of ERK1/2, but did not affect phosphorylation of ER ${\alpha}$ at $Ser^{118}$. It also increased cellular accumulation of cAMP, a hallmark of GPR30-mediated estrogen signaling. These data imply that tectoridin exerts its estrogenic effect mainly via the GPR30 and ERK-mediated rapid nongenomic estrogen signaling pathway. This property of tectoridin sets it aside from genistein where it exerts the estrogenic effects via both an ER-dependent genomic pathway and a GPR30-dependent nongenomic pathway.

완두 자엽세포의 소포체 내강에 축적된 저장 단백질에 대한 면역세포화학적 연구 (Immunocytochemical Investigation on the Intracisternal Accumulations of Storage Protein in Pea Cotyledon Cells)

  • 정병갑;박홍덕
    • Applied Microscopy
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    • 제31권2호
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    • pp.199-206
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    • 2001
  • 완두 자엽세포에 대한 저장단백질 과립의 발달은 단백질 저장 액포의 가장자리에 축적된 단백질의 fragmentation에 의해서 이루어지는 것으로 알려져 왔다. 그러나 최근 이 외에도 terminal dilation, transformation, denovo development등의 독립적인 과정이 각각 다른 시기에 관찰되므로서 단백과립의 발달은 이러한 여러 과정이 모두 나타나는 복합과정임이 알려졌다. 이러한 과정과는 별도로 종자발달의 이른시기에 소포체 내강에 축적되는 저장단백질과 여기서 발달하는 단백과립에 대하여 규명하고자 발달중인 종자의 자엽으로부터 단일 세포를 얻어서 면역세포 화학적 반응을 실시하였다. 그 결과 종자발달의 이른 시기에는 legumin이, 중간시기 이후 에는 vicilin이 축적되므로서 단백질이 축적된 소포체가 단백과립으로 발달하는 것으로 나타났다 소포체 내강에 존재하는 단백질인 $\alpha-Tip$은 비교적 늦은시기에, toneplast membrane protein인 PPase는 이른시기에 각각 면역 세포화학적 반응이 관찰되었다.

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흰쥐 부정소 내의 스테로이드 호르몬 수용체, $5{\alpha}$-reductase 그리고 Aromatase 발현에 미치는 EDS의 영향 (Effect of Ethane 1,2-Dimethane Sulfonate(EDS) on the Expression of Steroid Hormone Receptors, $5{\alpha}$-reductase and Aromatase in the Rat Epididymis)

  • 손혁준;이성호
    • 한국발생생물학회지:발생과생식
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    • 제11권3호
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    • pp.187-193
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    • 2007
  • Ethane 1,2-dimethane sulfonate(EDS)는 Leydig 세포의 선별적 사멸을 유도하는 약물로서 가역적인 테스토스테론 결핍 흰쥐를 만드는데 널리 사용된다. 부정소의 구조와 기능 유지는 크게 보아 정소에서 분비되는 테스토스테론에 의존적이지만, 테스토스테론으로부터 유도되는 dihydroxytestosterone(DHT)와 에스트로겐도 중요한 역할을 한다. 본 연구에서는 EDS 주사 후 7주까지 부정소에서의 스테로이드 호르몬 수용체, cyctochrome P450aromatase(P450arom)와 $5{\alpha}$-reductase의 유전자 발현 양상을 조사하였다. 성숙한 수컷 흰쥐($350{\sim}400\;g$)에 EDS를 1회 복강 주사하고(75 mg/kg i.p.) 주사 후 0, 1, 2, 3, 4, 5, 6, 7주가 경과한 날에 희생하였다. 표적 유전자들의 전사 활성은 반 정량적 역전사 중합효소 반응법(semi-quantitative RT-PCRs)으로 측정하였다. Estrogen receptor alpha($ER{\alpha}$) 전사 수준은 EDS 실험군에서 대조군에 비해 주사 1주후에 유의하게 상승했으나(P<0.01) 2주 후부터는 대조군과 유의적인 차이를 보이지 않았다. Estrogen receptor beta($ER{\beta}$)의 전사 수준은 주사 1주후 EDS 실험군에서 대조군에 비해 유의하게 증가했다가(P<0.05), 2주와 3주에는 감소하였고(P<0.05와 P<0.01), 4주와 6주까지는 변동폭을 보이다가 7주 후에는 대조군에 비해 증가하였다(P<0.05). Androgen receptor(AR) 전사 수준은 주사 2주 후에 유의하게 증가하다가(P<0.01) 3주 후부터는 대조군 수준으로 회복하였다. 반면, P450arom는 주사 1주 후부터 3주까지 급격하게 감소했다가(P<0.01 1주와 2주; P<0.05 3주), 4주에 대조군 수준으로 회복하였다. $5{\alpha}$-reductase type 2($5{\alpha}$-RT2)의 mRNA 수준은 4주 후 유의하게 증가했다가(P<0.01), 이후 대조군 수준으로 회복하였다. 본 연구는 EDS 주사가 성 스테로이드 호르몬 수용체들과 안드로겐 전환 효소들의 전사 활성에 가역적인 변화를 유도함을 보여준 것이다. EDS 주사 모델은 부정소의 생리 조절 기작을 이해하는데 유용할 것으로 사료된다.

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Prostaglandin $F_2\alpha$의 투여에 따른 자성 Rat의 혈중 Hormone 함량과 황체의 형태학적 변화 II. Prostaglandin$F_2\alpha$의 투여가 임신 Rat의 황체 구조에 미치는 영향 (Effects of Prostaglandin $F_2\alpha$ on the Hormone Concentration in Blood Plasma and Morphological Changes of Corpus Luteum in Female Rats II. The Effects of Prostaglandin $F_2\alpha$ on the Structure of the Corpups Luterum of the Pregnant Rat)

  • 변명대;조유정;성태수
    • 한국가축번식학회지
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    • 제16권1호
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    • pp.21-38
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    • 1992
  • The present study was carried out to investigate morphologic changes in the corpus luteum of the pregnant rat by electron microscope after administration of prostaglandin F2$\alpha$(PGF2$\alpha$). Pregnant rates were treated with PGF2$\alpha$(1,500$\mu\textrm{g}$/rat) and their corpura lutea were observed morphologically. The results obtained in this study were summarized as follows ; 1. The weight of the ovaries and corpura lutea were decreased slightly at 8~24 hours after PGF2$\alpha$ administratin but no significant differences were observed. 2. The number of corpora lutea and luteal cells decreased slightly at 12~48 hours and 18~24 hours after PGF2$\alpha$ tretment but there were no signifciant differences between control and treatment. 3. The weight of uterus and the unmber of embryo decreased slightly at 96 hours and at 18~96 hours after PGF2$\alpha$ administration but no significant differences were obtained. 4. In the electron microscopic observatons, lipid droplets which are electron dense and appear in the cytoplasm moderately increased in number after PGF2$\alpha$ treatment. The lipid droplets were surrounded by mitochodria and appeared in the autophagic vacuoles. 5. Moderated and high electron dense mitochondria which are round or elongated in shape showed pleomorphism from 3 hours after PGF2$\alpha$ treatment. Destruction of tubular of vesicular cristae was observed at 6 hours after the treatment. Dense body and myelin figures in matrix of mitochondria were also appeared. 6. Well-developed smooth endoplasmic reticulum(sER) showed tubular or vesicular cisternae. A number of whorl membranes containing ribosomes, mitochondria and lipid droplets were observed at 1.5 hour after treatment. sER was abundant in luteal cells at 12 hours were treatment. 7. Well-developed Golgi pparatus appeared obviously 6 hours and more prominently at 12 hours. Those Golgi vesicles were remarkably dilated. 8. Generally, a few rough endoplasmic reticulum (rER) were appeared after treatment and cisternae showed slight dilatation. No differences among the treatments were observed. However, slight dilation of cisternae was observed at 1.5 hours after treatment. 9. Ribosomes composed of free and polyribosomes were abundant before treatment but polyribosomes were appeared at 12 to 24 hours after treatment. 10. Intercellular space were slightly extended at 3 hours and markedly extended at 12 hours. Numerous microvillous protrusions were observed at these times. Membranous multivesicular structures and autophagic vacuoles were also appeared in the intercellular space. 11. At 3 hours after the treatment, autophagic vacuoles appeared in the cytoplasm of the cell. They increased in number with time and were observed to transfer to the intercellular space. Lysosomal dense body appeared in the cytoplasm and the inclusion body was also observed in nucleus at 12 to 24 hours after treatment.

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Assessment of Adipocyte Differentiation and Maturation-related Gene Expression in the Epididymal Fat of Estrogen Receptor α Knockout (ERαKO) Mouse during Postnatal Development Period

  • Cheon, Yong-Pil;Ko, CheMyong;Lee, Ki-Ho
    • 한국발생생물학회지:발생과생식
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    • 제24권4호
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    • pp.287-296
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    • 2020
  • The absence of functional estrogen receptor α (Esr1) results in an overgrowth of the epididymal fat, as observed in estrogen receptor α knockout (ERαKO) mouse. The present research was aimed to evaluate expression of various molecules associated with adipocyte differentiation and maturation in the epididymal fat of ERαKO mouse at several postnatal ages by using quantitative real-time polymerase chain reaction. The highest transcript levels of all molecules were detected at 12 months of postnatal age, except leptin which the mRNA level was increased at 5 months of age and was unchanged until 12 months of age. The expression levels of CCAAT enhancer binding protein (Cebp) alpha, androgen receptor, and lipoprotein lipase were decreased at 5 months of age but increased at about 8 months of age. The mRNA levels of Cebp gamma and sterol regulatory element binding transcription factor 1 remained steady until 8 months of age. Continuous increases of transcript levels during postnatal period were found in Cebp beta, estrogen receptor (ER) beta, fatty acid binding protein 4, and delta like non-canonical Notch ligand 1. The increases of peroxisome proliferator-activated receptor gamma and adiponectin mRNA levels were detected as early as 8 months of age. The levels of fatty acid synthase and resistin transcript at 5 and 8 months of age were lower than that at 2 months of age. These findings show the aberrant expression patterns of genes related to adipocyte differentiation and maturation in the postnatal epididymal fat pad by the disruption of ER alpha function.

한국인 자궁내막증 환자의 유전자 다형성 양상 (Genetic Polymorphisms in Patients with Endometriosis in the Korean Population)

  • 이경훈;최영민
    • Journal of Genetic Medicine
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    • 제6권2호
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    • pp.121-130
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    • 2009
  • 자궁내막증의 유전 소인을 감안하였을 때 관련 유전자 다형성 조사는 매우 중요한 의미를 갖는다. 현재까지 약 30여개의 한국인을 대상으로 한 결과를 조사하여 자궁내막증과 특정 유전자내 다형성과의 연관성을 파악하고자 하였다. 가장 의미있는 유전자 다형성은 한국인 자궁내막증 환자에서의 GSTT1, AhRR, ER-alpha, VEGF, AHSG, 그리고TNF-alpha 유전자 다형성이다. 다만 결과가 부분적으로 상충되기도 하여 추가 연구을 통해 결과 재현성을 증명해야 할 것으로 사료된다. 마지막으로 자궁내막증을 대상으로 유전자 연구에서의 추후 연구 방향을 제시하고자 한다.

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저온검출기의 열전도 연구 (Heat Flow Studies in Low Temperature Detectors)

  • 김일환;이민규;김용함
    • Progress in Superconductivity
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    • 제12권1호
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    • pp.41-45
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    • 2010
  • Low temperature micro-calorimeters have been employed in the field of high resolution alpha spectrometers. These alpha detectors typically consist of a superconducting or metal absorber and a temperature sensor. The temperature sensor can be a transition edge sensor (TES), a metallic magnetic calorimeter (MMC) or other low temperature detectors for an accurate measurement of temperature change due to an alpha particle absorption. We report a recent study of the heat flow between a replaceable absorber and a temperature sensor. A piece of gold foil in $2.4{\times}2.7{\times}0.03\;mm^3$ is used as an absorber. A $40\;{\mu}m$ diameter Au:Er paramagnetic sensor is attached to another small piece of gold foil in $400{\times}200{\times}30\;{\mu}m^3$ to serve as the temperature sensor. This sensor assembly, Au:Er and gold foil, is placed on a miniature SQUID susceptometer in a gradiometric configuration. The thermal connection between the absorber and the sensor was made with three gold bonding wires. The measured thermal conductance shows a linear dependence to the temperature. The values are in a good agreement with Wiedemann-Franz type thermal conductance of the gold wires.

Expression of the Receptor Genes of FSH, Estrogen- $\alpha$, $\beta$, Androgen, IGFI and TGF-$\beta$ during Fetal and Prepubertal Testicular Development in Mouse

  • Kim, Chul;Park, J.H.;Kim, S.J.;Seo, Y.J.;Do, B.R.;Roh, S.I.;Yoon, H.S.;Kim, E.S.
    • 한국발생생물학회:학술대회논문집
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    • 한국발생생물학회 2001년도 전기 제11차 학술대회 논문집
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    • pp.50-51
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    • 2001
  • In ultrastructure study of testis, Sertoli cells start to differentiate at 16 days of gestation. Transcripts of FSH receptor, IGF-I receptor, ER $\alphareceptor, $ $TGF-\beta$ receptor and androgen receptor were highly and initially expressed at 16 day of gestation. As results of in situ PCR at 16 day of gestation, transcripts of FSH, IGF-I receptor were detected in Sertoli cells and spermatogonia, whereas the receptors of $ER\alpha, $ $TGF-\beta$ and androgen were detected in Sertoli cells. Therefore, expression of FSH and estrogen $\alpha, $ androgen, IGF-I and $TGF-\alpha$ could play an important role during fetal and prepubertal testicular development by stage specific manner in mouse.