• Title/Summary/Keyword: ER1

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Laminar Flow Inhibits ER Stress-Induced Endothelial Apoptosis through PI3K/Akt-Dependent Signaling Pathway

  • Kim, Suji;Woo, Chang-Hoon
    • Molecules and Cells
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    • 제41권11호
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    • pp.964-970
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    • 2018
  • Atherosclerosis preferentially involves in prone area of low and disturbed blood flow while steady and high levels of laminar blood flow are relatively protected from atherosclerosis. Disturbed flow induces endoplasmic reticulum (ER) stress and the unfolded protein response (UPR). ER stress is caused under stress that disturbs the processing and folding of proteins resulting in the accumulation of misfolded proteins in the ER and activation of the UPR. Prolonged or severe UPR leads to activate apoptotic signaling. Recent studies have indicated that disturbed flow significantly up-regulated $p-ATF6{\alpha}$, $p-IRE1{\alpha}$, and its target spliced XBP-1. However, the role of laminar flow in ER stress-mediated endothelial apoptosis has not been reported yet. The present study thus investigated the role of laminar flow in ER stress-dependent endothelial cell death. The results demonstrated that laminar flow protects ER stress-induced cleavage forms of PARP-1 and caspase-3. Also, laminar flow inhibits ER stress-induced $p-eIF2{\alpha}$, ATF4, CHOP, spliced XBP-1, ATF6 and JNK pathway; these effects are abrogated by pharmacological inhibition of PI3K with wortmannin. Finally, nitric oxide affects thapsigargin-induced cell death in response to laminar flow but not UPR. Taken together, these findings indicate that laminar flow inhibits UPR and ER stress-induced endothelial cell death via PI3K/Akt pathway.

Endoplasmic Reticulum Stress Activates Hepatic Macrophages through PERK-hnRNPA1 Signaling

  • Ari Kwon;Yun Seok Kim;Jiyoon Kim;Ja Hyun Koo
    • Biomolecules & Therapeutics
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    • 제32권3호
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    • pp.341-348
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    • 2024
  • Endoplasmic reticulum (ER) stress plays a crucial role in liver diseases, affecting various types of hepatic cells. While studies have focused on the link between ER stress and hepatocytes as well as hepatic stellate cells (HSCs), the precise involvement of hepatic macrophages in ER stress-induced liver injury remains poorly understood. Here, we examined the effects of ER stress on hepatic macrophages and their role in liver injury. Acute ER stress led to the accumulation and activation of hepatic macrophages, which preceded hepatocyte apoptosis. Notably, macrophage depletion mitigated liver injury induced by ER stress, underscoring their detrimental role. Mechanistic studies revealed that ER stress stimulates macrophages predominantly via the PERK signaling pathway, regardless of its canonical substrate ATF4. hnRNPA1 has been identified as a crucial mediator of PERK-driven macrophage activation, as the overexpression of hnRNPA1 effectively reduced ER stress and suppressed pro-inflammatory activation. We observed that hnRNPA1 interacts with mRNAs that encode UPR-related proteins, indicating its role in the regulation of ER stress response in macrophages. These findings illuminate the cell type-specific responses to ER stress and the significance of hepatic macrophages in ER stress-induced liver injury. Collectively, the PERK-hnRNPA1 axis has been discovered as a molecular mechanism for macrophage activation, presenting prospective therapeutic targets for inflammatory hepatic diseases such as acute liver injury.

소포체스트레스에 의한 cAMP phosphodiesterase 7A1 유전자의 발현 (Expression of the cAMP Phosphodiesterase 7A1 Gene by Endoplasmic Reticulum Stress)

  • 권기상;권영숙;권오유
    • 생명과학회지
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    • 제22권2호
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    • pp.281-284
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    • 2012
  • 갑상선 배양세포(FRTL5)에서 ER stress에 의해서 ER chaperone (Bip, ERp29, Calnexin and PDI), ER stress sensor (PERK, ATF6 and Ire1)와 cAMP phosphodiesterase 7A1 (cAMP PDE7A1) 유전자발현이 증가하는 것을 알았다. 세포배양배지에서 A23187을 제거하면 cAMP PDE7A1 유전자발현이 회복되지만, thapsigagin의 경우는 회복되지 않았다. 그리고 A23187과 TSH를 함께 처리한 경우는 아주 강하게 cAMP PDE7A1 유전자의 발현이 억제되었다. 이 같은 결과는 ER stress에 의해서 cAMP PDE7A1 유전자발현이 상승 발현된다는 첫 보고이다.

Estrogen receptor β stimulates Egr-1 transcription via MEK1/Erk/Elk-1 cascade in C6 glioma cells

  • Kim, Ji-Ha;Jeong, Il-Yeup;Lim, Yoong-Ho;Lee, Young-Han;Shin, Soon-Young
    • BMB Reports
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    • 제44권7호
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    • pp.452-457
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    • 2011
  • The Egr-1 is an immediate early response gene encoding a transcription factor that functions in the regulation of cell growth, differentiation, and apoptosis. Estrogen has diverse physiological effects, including cellular proliferation and neuroprotection against brain injury. There are two types of estrogen receptors (ERs), $ER{\alpha}$ and $ER{\beta}$. $ER{\alpha}$-induced Egr-1 expression has been extensively studied; however, the role of $ER{\beta}$ is yet not known. In the present study, we investigated whether or not $ER{\beta}$ induces Egr-1 expression in C6 rat glioma cells, which express $ER{\beta}$ but not $ER{\alpha}$. Our results show that $ER{\beta}$ promoted up-regulation of Egr-1 expression via a non-genomic mechanism involving the Raf/MEK1/Erk/Elk-1 signaling cascade.

Er:YAG 레이저를 이용한 법랑질 표면처리가 치면열구전색제의 미세누출에 미치는 영향 (INFLUENCE OF THE ENAMEL TREATMENT WITH ER:YAG LASER ON THE MICROLEAKAGE OF PIT AND FISSURE SEALANT)

  • 이지현;김재문;김신;정태성
    • 대한소아치과학회지
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    • 제33권2호
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    • pp.192-200
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    • 2006
  • 본 연구는 Er:YAG레이저를 이용한 법랑질의 표면처리가 치면열구전색제의 미세누출에 미치는 영향을 알아보기 위해서 시도되었다. 먼저 법랑질 표면 처리에 적절한 Er:YAG레이저 조사 수준을 알아보기 위해, 치면열구에 50 mJ에서 300 mJ까지 3 Hz로 레이저를 조사하고, 주사전자현미경으로 표면 변화를 관찰하였다. 교정 목적으로 발거된 건전한 소구치 36개를 치면열구전색 전 법랑질 처리 방법에 따라 아무런 처리 없는 군(1군), 전통적인 산부식 시행한 군(2군), Er:YAG 레이저를 조사한 군(3군), Er:YAG 레이저 조사 후 산부식 시행한 군(깊군)으로 나누었다. 치면열구전색 후 1000회의 열순환을 시행하였고, Rhodamine B를 이용해 치아를 염색하였다. 각 치아를 협설 방향으로 절단하여 1mm 두께의 시편 3개를 만들었으며, 총 108개의 시편 (각 군당 27개)을 얻었고, 형광현미경으로 관찰하여 다음과 같은 결론을 얻었다. 1. 주사전자현미경 관찰 결과 50 mJ, 3 Hz로 Er:YAG 레이저를 조사하였을 때 산부식과 유사한 법랑질 표면 변화를 관찰할 수 있었으며, 조사 에너지가 증가할수록 법랑질 표면의 용해와 재결정화 및 균열이 관찰되었다. 2. 치면열구전색의 미세누출도 1>3>4>2 군의 순으로 많이 나타났었다. 1, 3, 4군은 미세누출토에서 상호 차이를 나타내지 않았으나(p>0.05), 2군은 1, 3군에 비해 유의하게 적었다(p<0.05). 이상의 결과로 볼 때, 치면열구전색시 미세누출의 감소에 있어 Er:YAG레이저 조사보다 전통적인 산부식이 우수하다 생각되며, Er:YAG 레이저의 조사조건에 대한 더 많은 연구가 필요할 것으로 사료된다.

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Zn-Pr-Co-Cr-Er 산화물계 바이스터의 전기적 성질 (Electrical Properties of Zn-Pr-Co-Cr-Er Oxides-based Varistors)

  • 남춘우;류정선
    • 한국전기전자재료학회논문지
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    • 제14권5호
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    • pp.362-369
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    • 2001
  • The electrical properties of varistors consisting of Zn-Pr-Co-Cr-Er oxides were investigated in the Er$_2$O$_3$content range of 0.0 to 2.0 mol%. the varistors without Er$_2$O$_3$ exhibited a relatively low nonlinearity, which was 14.24 in the nonlinear exponent and 21.47 $\mu$A in the leakage current. However, the varistors with Er$_2$O$_3$ sintered at 1335$^{\circ}C$ for 1h exhibited very high nonlinear exponent of 70, in particular, reaching a maximum value of 78.05 in 2.0 mol% Er$_2$O$_3$, and those sintered at 1335$^{\circ}C$ for 2h exhibited the nonlinear exponent close to 50, in particular, reaching a maximum value of52.76 in 0.5 mol% Er$_2$O$_3$. The others except for 0.5 mol% Er$_2$O$_3$-added varistors exhibited very high instability resulting in a thermal runaway within a short time, even a weak DC stress. Increasing soaking time decreased the nonlinearity, but increased the stability. The varistors containing 0.5mol% Er$_2$O$_3$ sintered for 2h exhibited excellent stability, in which the variation rate of the varistor voltage and nonlinear exponent was -1.70% and -7.15%, respectively, under more severe DC stress such as (0.80 V$_{1mA}$/9$0^{\circ}C$/12h)+(0.85 V$_{1mA}$/115$^{\circ}C$/12h)+(0.90 V$_{1mA}$/12$0^{\circ}C$/12h)+(0.95 V$_{1mA}$/1$25^{\circ}C$/12h)+(0.95 V$_{1mA}$/15$0^{\circ}C$/12h).TEX>/12h).

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Endoplasmic recticulum stress와 관련된 유전자기능과 전사조절인자의 In silico 분석 (In Silico Analysis of Gene Function and Transcriptional Regulators Associated with Endoplasmic Recticulum (ER) Stress)

  • 김태민;여지영;박찬선;이문수;정명호
    • 생명과학회지
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    • 제19권8호
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    • pp.1159-1163
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    • 2009
  • ER stress에 관련된 유전자의 기능변화와 전사조절인자 분석하기 위해 ER stress를 유도한 간세포에서 expression microarray로 유전자 발현을 확보한 후 GSECA로 분석하였다. ER stress가 유도되면, ER에 주어지는 과도한 부하를 감소시키는 기능들이 증가하는 반면, ER stress가 더 증가함에 따라 ATP 생성이나 DNA repair, 더 나아가 세포분열의 기능이 감소하는 등 세포가 damage을 받음을 알 수 있었다. ER stress에 관련된 전사조절인자로는 FOX04, AP-1, FOX03, HNF4, IRF-1, GATA 등의 전사조절인자들이 ER stress에 의해 발현이 증가하는 유전자들의 promoter에 공통적으로 존재하였으며, E2F, Nrf-1, Elk-1, YY1, CREB, MTF-1, STAT-1, ATF 등의 전사인자들이 발현이 감소하는 유전자들의 promoter에서 공통적으로 존재하여, 이들의 전사인자들이 ER stress에 의한 유전자의 발현조절에 중요한 역할을 하는 전사조절인자임을 알 수 있었다.

ER인서트를 이용한 Hull Mount에서의 진동저감에 관한 연구 (Vibration reduction in a Hull mount using the ER inserts)

  • Kim, Ji-Seon;Kim, Jae-Hwan;Park, Seung-Bok;Kim, Kung-Su
    • 한국소음진동공학회:학술대회논문집
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    • 한국소음진동공학회 2002년도 추계학술대회논문초록집
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    • pp.348.1-348
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    • 2002
  • This paper deals with the vibration reduction of the hull mount system of ship structures brought by ER smart structures. The hull mount is used to isolate the vibration form the immersed structures. Utilizing the tunable characteristics of ER fluids, ER insert are made In the hull mountint structure. Different types of ER inserts are proposed and the vibration characteristics are investigated. (omitted)

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Do Clinical Features and Survival of Single Hormone Receptor Positive Breast Cancers Differ from Double Hormone Receptor Positive Breast Cancers?

  • Ng, Char-Hong;Pathy, Nirmala Bhoo;Taib, Nur Aishah;Ho, Gwo-Fuang;Mun, Kein-Seong;Rhodes, Anthony;Looi, Lai-Meng;Yip, Cheng-Har
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권18호
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    • pp.7959-7964
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    • 2014
  • The significance of the single hormone receptor positive phenotype of breast cancer is still poorly understood. The use of hormone therapy has been found to be less effective for this type, which has a survival outcome midway between double positive and double negative phenotypes. The aim of this study was to investigate differences in patient and tumor characteristics and survival between double-receptor positive (ER+PR+), double receptor negative (ER-PR-) and single receptor positive (ER+PR- and ER-PR+) breast cancer in an Asian setting. A total of 1,992 patients with newly diagnosed stage I to IV breast cancer between 2003 and 2008, and where information on ER and PR were available, were included in this study. The majority of patients had ER+PR+ tumors (n=903: 45.3%), followed by 741 (37.2%) ER-PR-, 247 (12.4%) ER+PR-, and 101 (5.1%) ER-PR+ tumors. Using multivariate analysis, ER+PR- tumors were 2.4 times more likely to be grade 3 compared to ER+PR+ tumors. ER+PR- and ER-PR+ tumors were 82% and 86% respectively less likely to be grade 3 compared with ER-PR- tumors. ER-PR+ tumours were associated with younger age. There were no survival differences between patients with ER+PR+ and ER-PR+ tumors. However, ER+PR- tumors have poorer survival compared with ER+PR+ tumours. ER-PR- tumours had the worst survival. Adjuvant hormonal therapy with tamoxifen was found to have identical survival advantage in patients with ER+PR+ and ER-PR+ tumors whereas impact was slightly lower in patients with ER+PR- tumors. In conclusion, we found ER+PR- tumors to be more aggressive and have poorer survival when compared to ER+PR+ tumors, while patients with ER-PR+ tumours were younger, but had a similar survival to their counterparts with ER+PR+ tumours.

졸겔법으로 제조한 ErMnO3 박막의 강유전 특성 (Ferroelectric Properties of ErMnO3 Thin Film Prepared by Sol-gel Method)

  • 김유택;김응수;채정훈;류재호
    • 한국세라믹학회지
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    • 제39권9호
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    • pp.829-834
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    • 2002
  • $Er(NO_3)_3{\codt}5H_2O,\;Mn(CH_3CO_2)_2{\cdot}4H_2O$를 출발원료로 사용하여 졸-겔 법으로 Si(100) 기판 위에 코팅된 $ErMnO_3$ 박막의 강유전 특성에 관하여 연구하였다. $ErMnO_3$ 박막은 800$^{\circ}C$에서 결정화가 시작되었으며, (001)로 우선 배향된 $ErMnO_3$ 박막을 얻을 수 있었다. 본 실험에서 800$^{\circ}C$에서 1 h 열처리하여 얻은 $ErMnO_3$ 박막은 1∼100 KHz의 주파수 범위에서 유전 상수(k)는 26, 유전 손실(tan ${\delta}$)은 0.032의 값을 나타내었으며, 이때 $ErMnO_3$ 박막의 입자 크기는 10∼30 nm이었다. 강유전 특성은 (001) 배향성이 증가할수록 잔류 분극 값이 증가하였으며, 800$^{\circ}C$에서 1시간 열처리하여 $ErMnO_3$ 박막의 잔류 분극 값($P_r$)은 400 nC/$cm^2$를 나타내었다. 또한 열처리 시간이 증가할수록 치밀하고 균일한 박막을 얻어 낮은 항전계 ($E_c$) 값을 가졌다.