• Title/Summary/Keyword: ER-stress

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[ ${\alpha}$ ]Synuclein Induces Unfolded Protein Response Via Distinct Signaling Pathway Independent of ER-membrane Kinases

  • Kang, Shin-Jung;Shin, Ki-Soon;Kim Kwon, Yun-Hee
    • Animal cells and systems
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    • v.10 no.3
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    • pp.115-120
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    • 2006
  • Parkinson's disease (PD) is a neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Mutations in ${\alpha}$-synuclein have been causally linked to the pathogenesis of hereditary PD. In addition, it is a major component of Lewy body found in the brains of sporadic cases as well. In the present study, we examined whether overexpression of wild type or PD-related mutant ${\alpha}$-synuclein induces unfolded protein response (UPR) and triggers the known signaling pathway of the resulting endoplasmic reticulum (ER) stress in SH-SY5Y cells. Overexpression of wild type, A30P, and A53T ${\alpha}$-synuclein all induced XBP-1 mRNA splicing, one of the late stage UPR events. However, activation of ER membrane kinases and upregulation of ER or cytoplsmic chaperones were not detected when ${\alpha}$-synuclein was overexpressed. However, basal level of cytoplsmic calcium was elevated in ${\alpha}$-synuclein-expressing cells. Our observation suggests that overexpression of ${\alpha}$-synuclein induces UPR independent of the known ER membrane kinase-mediated signaling pathway and induces ER stress by disturbing calcium homeostasis.

A Study on Bingham Characteristics of Particle Dispersive Electro-Rheological Fluid (입자분산계 ER유체의 빙햄특성 고찰)

  • 장성철;이선의;김태형;박종근;염만오
    • Proceedings of the Korea Committee for Ocean Resources and Engineering Conference
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    • 2000.10a
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    • pp.178-183
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    • 2000
  • Electrorheological(ER) effect on the dispersive system of polarizable fine powder/dielectric oil has been investigated. The electrical and rheological properties of zeolite and starch based ER fluid were reported. The ER fluids were constructed by mixing zeolite and starch power with two different dielectric oils. Yield stress of the fluids were measured on the couette cell type rheometer as a function of electric fields, particle concetrations, and temperatures. The electric field is applied by high voltage DC power supply. The outer cup is connected to positive electrode(+) and the bob becomes ground(-). And the temperatures the viscosity(or shear stress) versus shear rates were measured. In this experiment shear rates were increased from 0 to $200s^{-1}$ in 2 minutes.

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Electrorheology and universal yield stress function of semiconducting polymer suspensions

  • Choi, Hyoung-J.;Cho, Min-S.;Kim, Ji-W.
    • Korea-Australia Rheology Journal
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    • v.13 no.4
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    • pp.197-203
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    • 2001
  • We reported on the eletrorheological (ER) properties of several semiconducting polymers including poly (p-phenylene) (PPP), poly (acene quinone) radicals (PAQRs), microencapsulated polyaniline (MPANI) and polyaniline (PANI) those we synthesized. The yield stress dependence on electric field strength for the ER fluids using these semiconducting polymers was mainly examined. The yield stress, which is an important design parameter for ER fluids, was observed to satisfy a universal scaling function, allowing that yield stress data for all the ER fluids examined in this study collapse onto a single curve for a broad range of electric field strengths. The proposed scaling function incorporates both the polarization and conductivity models.

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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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Role of E2F1 in Endoplasmic Reticulum Stress Signaling

  • Park, Kyung Mi;Kim, Dong Joon;Paik, Sang Gi;Kim, Soo Jung;Yeom, Young Il
    • Molecules and Cells
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    • v.21 no.3
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    • pp.356-359
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    • 2006
  • The transcription factor E2F1 coordinates cell cycle progression and induces apoptosis in response to DNA damage stress. Aside from DNA damage, the role of E2F1 in the endoplasmic reticulum (ER) stress signaling pathways is unclear. We found that $E2F1^{-/-}$ murine embryonic fibroblasts (MEFs) are resistant to apoptosis triggered by the ER stress inducer thapsigargin. In addition, E2F1 deficiency results in enhanced phosphorylation of eukaryotic translation initiation factor $2{\alpha}$ ($elF2{\alpha}$). These results therefore indicate that E2F1 deficiency increases phosphorylation of $elF2{\alpha}$ in response to ER stress triggered by thapsigargin, and suggest that the reduction in ER stress-induced apoptosis in E2F1-deficient cells is related to the high level of $elF2{\alpha}$ phosphorylation.

1,25-dihydroxyvitamin D3 affects thapsigargin-induced endoplasmic reticulum stress in 3T3-L1 adipocytes

  • Dain Wi;Chan Yoon Park
    • Nutrition Research and Practice
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    • v.18 no.1
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    • pp.1-18
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    • 2024
  • BACKGROUND/OBJECTIVES: Endoplasmic reticulum (ER) stress in adipose tissue causes an inflammatory response and leads to metabolic diseases. However, the association between vitamin D and adipose ER stress remains poorly understood. In this study, we investigated whether 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) alleviates ER stress in adipocytes. MATERIALS/METHODS: 3T3-L1 cells were treated with different concentrations (i.e., 10-100 nM) of 1,25(OH)2D3 after or during differentiation (i.e., on day 0-7, 3-7, or 7). They were then incubated with thapsigargin (TG, 500 nM) for an additional 24 h to induce ER stress. Next, we measured the mRNA and protein levels of genes involved in unfold protein response (UPR) and adipogenesis using real-time polymerase chain reaction and western blotting and quantified the secreted protein levels of pro-inflammatory cytokines. Finally, the mRNA levels of UPR pathway genes were measured in adipocytes transfected with siRNA-targeting Vdr. RESULTS: Treatment with 1,25(OH)2D3 during various stages of adipocyte differentiation significantly inhibited ER stress induced by TG. In fully differentiated 3T3-L1 adipocytes, 1,25(OH)2D3 treatment suppressed mRNA levels of Ddit3, sXbp1, and Atf4 and decreased the secretion of monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-α. However, downregulation of the mRNA levels of Ddit3, sXbp1, and Atf4 following 1,25(OH)2D3 administration was not observed in Vdr-knockdown adipocytes. In addition, exposure of 3T3-L1 preadipocytes to 1,25(OH)2D3 inhibited transcription of Ddit3, sXbp1, Atf4, Bip, and Atf6 and reduced the p-alpha subunit of translation initiation factor 2 (eIF2α)/eIF2α and p-protein kinase RNA-like ER kinase (PERK)/PERK protein ratios. Furthermore, 1,25(OH)2D3 treatment before adipocyte differentiation reduced adipogenesis and the mRNA levels of adipogenic genes. CONCLUSIONS: Our data suggest that 1,25(OH)2D3 prevents TG-induced ER stress and inflammatory responses in mature adipocytes by downregulating UPR signaling via binding with Vdr. In addition, the inhibition of adipogenesis by vitamin D may contribute to the reduction of ER stress in adipocytes.

Electrorhelological Properties of Monodispersed Submicron-sized Hollow Polyaniline Adipate Suspension

  • Sung, Bo-Hyun;Choi, Ung-Su
    • KSTLE International Journal
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    • v.6 no.1
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    • pp.28-32
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    • 2005
  • The electrorheoloRical (ER) fluids are composed of a colloidal dispersion of polarizable particles in insulating oil, and it's the rheological property changes by the applied electric field. These changed are reversible and occur fast within a fewmilliseconds. The ER properties of the ER fluid such as increment of viscosity and yield stress come from the particle chain structure induced by electric fleld. When formulating the ER fluid for a speciflc application, some requirement must besatisfled, which are high yield stress under electric field, rapid response, and dispersion stability. While this characteristic makes valuable ER fluids in valious industrial applications, their lung term and quiescent application has been limited because ofproblems with particle sedimentation. In an effort to overcome sedimentation problem of ER fluids, the anhydrous ER materials of monodispersed hollow polyaniline (PANI) and adipate derivative respectively with submicron-sized suspension providing wide operating temperature range and other advantage were synthesized in a four-step procedure. The ER fluidswere characterized by FT-lR, TGA, DLS, SEM, and TEM. Stability of the suspensions was examined by an UV spectroscopy.The rheological and electrical properties of the suspension were investigated Couette-type rheometer with a high voltagegenerator, current density, and conductivity. And the behavior of ER suspensions was observed by a video camera attached toan optical microscope under 3kV/mm. The suspensions showed good ER properties, durability, and particle dispersion.

Inhibitory Effects of Ethanol Extract of Rhodiola Sacra on Endoplasmic Reticulum Stress in Neuro-2A Cells (설치류 Neuro-2A 신경세포에서 홍경천 에탄올 추출물의 소포체 스트레스 억제효과)

  • Jo, Nam-Eun;Song, Young-soon
    • Journal of Digital Convergence
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    • v.17 no.8
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    • pp.265-270
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    • 2019
  • Growing evidence suggests that mediating apoptotic cell death of ER stress plays an important role in pathological development of neurodegenerative diseases including Alzheimer's disease. The ethanol extract of Rodiola sacra (ERS) investigates whether ER stress protects neuroinvasive neuro-2A cells from homocysteine (Hcy) cell death and ER stress. In neuronal cells, Hcy markedly decreased the viability of the cells and induced the death of Annexin V-positive cells as confirmed by MTT assay. The Hcy cell viability and apoptotic loss pretreated with ERS were attenuated, and Hcy showed stress in the expression of C / EBP homologous protein, 78-kDa glucose regulatory protein and the junction of X-box binding protein-1 (xbp1) mRNA. ESR decreased Hcy-induced mRNA binding, GRP78 and CHOP cells induced Hcy-induced ER stress and apoptosis, and Western blotting revealed expression of heme oxygenase-1 and HO-1 enzyme activity Inhibition is indicative of therapeutic value for neurodegenerative diseases such as decreased cell death by hemin.

Neuroprotective Effects of Parkin and Bcl-2 against Dieldrin-induced Endoplasmic Reticulum Stress (디엘드린 유도성 소포체 스트레스에서의 parkin과 Bcl-2의 신경보호 효과)

  • Seo, Jeong-Yeon;Kim, Jae-Sung;Kim, Do Kyung;Chun, Hong Sung
    • Journal of Life Science
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    • v.32 no.10
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    • pp.771-777
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    • 2022
  • Dopaminergic (DA) cell death in Parkinson's disease (PD) has been attributed to multiple, distinct genetic and environmental factors. In rare familial PD loss of parkin function mutations play a key role in nigral DA neuron-specific pathogenesis primarily via endoplasmic reticulum (ER) stress. In more prevalent sporadic PD, environmental exposure to pesticides has a significant epidemiological role. However, it is largely unknown how environmental exposure to xenobiotics is etiologically linked with the known etiology in familial PD. In the present study biochemical evidence for a common pathogenic mechanism between sporadic and familial PD has been identified employing the recently characterized mesencephalic DA cell line, N27-A. Dieldrin, an organochlorine pesticide epidemiologically implicated in sporadic PD, induced the markers of ER stress response such as a chaperone BiP/Grp78, heme oxygenase-1 and especially, parkin. Accordingly, dieldrin activated the ER resident Caspase-12, a mediator of ER stress-specific apoptosis, during cell death of N27-A cells. Of great interest the dieldrin-induced DA neuronal cell death was synergistically rescued by the overexpression of ER resident neuroprotective proteins, parkin and Bcl-2. The present findings implicate that accumulation of ER stress could be one of common pathogenic mechanisms in idiopathic and familial PD, and some ER proteins, such as parkin and Bcl-2 may effectively attenuate ER stress-mediated N27-A DA cell death.

${\alpha}$-Mangostin Reduced ER Stress-mediated Tumor Growth through Autophagy Activation

  • Kim, Sung-Jin;Hong, Eun-Hye;Lee, Bo-Ra;Park, Moon-Ho;Kim, Ji-Won;Pyun, A-Rim;Kim, Yeon-Jeong;Chang, Sun-Young;Chin, Young-Won;Ko, Hyun-Jeong
    • IMMUNE NETWORK
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    • v.12 no.6
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    • pp.253-260
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    • 2012
  • ${\alpha}$-Mangostin is a xanthon derivative contained in the fruit hull of mangosteen (Garcinia mangostana L.), and the administration of ${\alpha}$-Mangostin inhibited the growth of transplanted colon cancer, Her/CT26 cells which expressed Her-2/neu as tumor antigen. Although ${\alpha}$-Mangostin was reported to have inhibitory activity against sarco/endoplasmic reticulum $Ca^{2+}$ ATPase like thapsigargin, it showed different activity for autophagy regulation. In the current study, we found that ${\alpha}$-Mangostin induced autophagy activation in mouse intestinal epithelial cells, as GFP-LC3 transgenic mice were orally administered with 20 mg/kg of ${\alpha}$-Mangostin daily for three days. However, the activation of autophagy by ${\alpha}$-Mangostin did not significantly increase OVA-specific T cell proliferation. As we assessed ER stress by using XBP-1 reporter system and phosphorylation of $eIF2{\alpha}$, thapsigargin-induced ER stress was significantly reduced by ${\alpha}$-Mangostin. However, coadministration of thapsigargin with ${\alpha}$-Mangostin completely blocked the antitumor activity of ${\alpha}$-Mangostin, suggesting ER stress with autophagy blockade accelerated tumor growth in mouse colon cancer model. Thus the antitumor activity of ${\alpha}$-Mangostin can be ascribable to the autophagy activation rather than ER stress induction.