• 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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    • v.41 no.11
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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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    • v.32 no.3
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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.

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

  • Kwon, Ki-Sang;Kwon, Young-Sook;Kwon, O-Yu
    • Journal of Life Science
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    • v.22 no.2
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    • pp.281-284
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    • 2012
  • This study demonstrated that upregulation of gene expression of endoplasmic reticulum (ER) stress chaperones (Bip, ERp29, calnexin, and PDI), ER stress sensors (PERK, ATF6, and Ire1), and cAMP phosphodiesterase 7A1 (cAMP PDE7A1) was induced by ER stresses in FRTL5 cells. While removing A23187 from the culture medium restored upregulation of cAMP PDE7A1 gene expression, removal of thapsigargin did not recover its expression. In addition, cAMP PDE7A1 gene expression was strongly inhibited by treatment with A23187 combined with thyroid stimulating hormone (TSH). The results are the first to show that ER stress induces cAMP PDE7A1 gene expression.

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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    • v.44 no.7
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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.

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

  • Lee, Ji-Hyun;Kim, Jae-Moon;Kim, Shin;Jeong, Tae-Sung
    • Journal of the korean academy of Pediatric Dentistry
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    • v.33 no.2
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    • pp.192-200
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    • 2006
  • The aim of this study was to assess the microleakage underneath a pit and fissure sealant bonded to occlusal surfaces treated by Er:YAG laser To determine the most effective energy density of laser, fourteen specimens were irradiated from 50mJ to 300mJ at 3Hz. After irradiation, the lased specimens were observed under the scanning electron microscope. Thirty six non-carious extracted premolars were randomly assigned to four groups of nine teeth: group 1, no treatment on the occlusal surface; group 2, acid etching for 15 seconds; group 3, Er:YAG laser irradiation; group 4, acid etching followed by Er:YAG laser irradiation. The pits and fissures were sealed with unfilled sealant(Helioseal F) and the specimen teeth were thermo-cycled, immersed in 2% Rhodamine B solution, longitudinally sectioned and analyzed for microleakage with fluorescent microscope. The results were as follows: 1. Er:YAG lased surfaces with 50mJ, 3Hz showed a similar pattern of irregularity with acid etched enamel surfaces 2. The mean microleakage score increased in the order of group 2, 4, 3 and 1. There was no significant difference among group 1, 3 and 4(p>0.05), however group 2 showed significantly less microleakage compared with group 1 and 3. Conclusively, the laser irradiation seemed not enough to replace the acid etching for proper retention of pit and fissure sealants.

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

  • 남춘우;류정선
    • Journal of the Korean Institute of Electrical and Electronic Material Engineers
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    • v.14 no.5
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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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In Silico Analysis of Gene Function and Transcriptional Regulators Associated with Endoplasmic Recticulum (ER) Stress (Endoplasmic recticulum stress와 관련된 유전자기능과 전사조절인자의 In silico 분석)

  • Kim, Tae-Min;Yeo, Ji-Young;Park, Chan-Sun;Rhee, Moon-Soo;Jung, Myeong-Ho
    • Journal of Life Science
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    • v.19 no.8
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    • pp.1159-1163
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    • 2009
  • It has been postulated that endoplasmic (ER) stress is involved in the development of several diseases. However, the detailed molecular mechanisms have not been fully understood. Therefore, we characterized a genetic network of genes induced by ER stress using cDNA microarray and gene set expression coherence analysis (GSECA), and identified gene function as well as several transcription regulators associated with ER stress. We analyzed time-dependent gene expression profiles in thapsigargin-treated Sk-Hep1 using an oligonucleotide expression chip, and then selected functional gene sets with significantly high expression coherence which was processed into functional clusters according to the expression similarities. The functions related to sugar binding, lysosome, ribosomal protein, ER lumen, and ER to golgi transport increased, whereas the functions with mRNA processing, DNA replication, DNA repair, cell cycle, electron transport chain and helicase activity decreased. Furthermore, functional clusters were investigated for the enrichment of regulatory motifs using GSECA, and several transcriptional regulators associated with regulation of ER-induced gene expression were found.

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

  • Kim, Ji-Seon;Kim, Jae-Hwan;Park, Seung-Bok;Kim, Kung-Su
    • Proceedings of the Korean Society for Noise and Vibration Engineering Conference
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    • 2002.11a
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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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    • v.15 no.18
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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.

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

  • Kim, Yoo-Taek;Kim, Eung-Soo;Chae, Jung-Hoon;Ryu, Jae-Ho
    • Journal of the Korean Ceramic Society
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    • v.39 no.9
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    • pp.829-834
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    • 2002
  • Ferroelectric properties of $ErMnO_3$ thin films deposited on Si(100) substrate using Sol-gel process with metal salts were investigated. $ErMnO_3$ thin films with a (001) preferred orientation were crystallized at 800$^{\circ}C$. The $ErMnO_3$ thin film post-annealed at 800$^{\circ}C$ for 1 h showed the dielectric constant(k) of 26 and the dielectric loss(tan ${\delta}$) of 0.032 at the frequency range from 1 to 100 KHz. The grain size of $ErMnO_3$ thin film post-annealed at 800 for 1 h was 10∼30 nm. The remanent polarization($P_r$) of the $ErMnO_3$ thin films increased with increasing (001) preferred orientation. The $ErMnO_3$ thin films post-annealed at 800$^{\circ}C$ for 1 h showed the remanent polarization($P_r$) of 400 nC/$cm^2$, with the increase of post-annealing time at 800$^{\circ}C$, the coercive field($E_c$) of thin films was lowered because the dense and homogeneous thin films were obtained.