• Tribology and Lubricants
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• 제18권1호
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• pp.16-23
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• 2002

For increasing the yield stress of ER fluids, the compressing ER electrode was developed and the compressing electrorheological (ER) behavior of anhydrous ER fluids in silicone oil of phosphorous ester cellulose powder was investigated. Under constant electric field, not only the current density but also the yield stress of anhydrous ER fluids were studied as varying the compressing length of ER electrode distance. From the experimental results the compressing of ER electrode had a large influence to the ER properties of anhydrous ER fluids. The current density was proportional to the compressing length of ER electrode under constant electric field and volume fraction also tile compressing yield stress was proportional to the volume fraction of dispersed particles under constant electric field and compressing length. When the ER electrode was compressed with 150mm after charging the electric field, 4 kV, tile yield stress of phosphoric ester cellulose ER fluids increased to thirteen times comparing with the yield stress measured at normal electrode.

• 한국윤활학회:학술대회논문집
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• 한국윤활학회 2001년도 제34회 추계학술대회 개최
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• pp.138-145
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• 2001

For increasing the yield stress of ER fluids, the compressing ER electrode was developed and the compressing electrorheological (ER) behavior of anhydrous ER fluids in silicone oil of phosphorous ester cellulose powder was investigated. Under constant electric field, not only the current density but also the yield stress of anhydrous ER fluids were studied as varying the compressing length of compressing ER electrode. From the experimental results, the compressing of ER electrode had a large influence to the ER properties of anhydrous ER fluids. The current density was proportional to the compressing length of ER electrode under constant electric field and volume fraction also the compressing yield stress was proportional to the volume fraction of dispersed particles under constant electric field and compressing length. When the ER electrode was compressed with 150mm after charging the electric field, 4 kV, the yield stress of phosphoric ester cellulose ER fluids increased to thirteen times comparing with the yield stress measured at normal electrode.

• Molecules and Cells
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• 제41권8호
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• pp.705-716
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• 2018

The endoplasmic reticulum (ER) is a critical organelle for protein synthesis, folding and modification, and lipid synthesis and calcium storage. Dysregulation of ER functions leads to the accumulation of misfolded- or unfolded-protein in the ER lumen, and this triggers the unfolded protein response (UPR), which restores ER homeostasis. The UPR is characterized by three distinct downstream signaling pathways that promote cell survival or apoptosis depending on the stressor, the intensity and duration of ER stress, and the cell type. Mammalian cells express the UPR transducers IRE1, PERK, and ATF6, which control transcriptional and translational responses to ER stress. Direct links between ER stress and immune responses are also evident, but the mechanisms by which UPR signaling cascades are coordinated with immunity remain unclear. This review discusses recent investigations of the roles of ER stress in immune responses that lead to differentiation, maturation, and cytokine expression in immune cells. Further understanding of how ER stress contributes to the pathogenesis of immune disorders will facilitate the development of novel therapies that target UPR pathways.

• 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.

• 생명과학회지
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• 제17권6호통권86호
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• pp.847-858
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• 2007

ER-Golgi 분비 경로를 통해서 정확한 구조를 가지면서 post-translational modification 과정을 거친 재조합 단백질의 발현을 최대화하는 것은 ER stress반응에 대한 연구의 중요한 계기가 된다. 세포가 스트레스를 받지 않는 상태라도 ER stress signaling은 재조합 단백질의 생산량을 제한하고 품질을 떨어뜨리는 여러 가지 조건을 만들게 된다. ER stress signaling을 막는 여러 가지 방법들이 제시되고 있으며 표 2는 이러한 방법들 중 일부를 나타내고 있다. 일반적으로는 pro-survival 경로에 관련되어 있는 인자를 촉진하고 pro-apoptosis에 관련되어 있는 인자를 억제하는 것들이다. 그러나 ER stress 반응은 매우 복잡하고 적응과 사멸 기작(adaptation and elimination mechanism)의 중간 역할을 하기 때문에 ER stress에 관련된 주요 인자를 산업적으로 응용하기 위해선 이들의 기능에 대해 보다 깊은 연구가 이루어져야 한다. 현재까지 재조합단백질의 생산량을 최대한으로 높이는 방법은 ER stress 반응이 생기지 않도록 fed-batch process를 개선하고 세포 사멸 기작을 조절하며 단백질의 glycosylation 처리를 하는 것이다.

• 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.

• 대한의생명과학회지
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• 제11권2호
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• pp.135-141
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• 2005

A Jopock (Jpk), a trans-acting factor associating with the position-specific regulatory element of murine Hoxa-7, has shown to have a toxicity to both prokaryotic and eukaryotic cells when overexpressed. Since Jpk protein harbors a transmembrane domain and a putative endoplasmic reticulum (ER)-retention signal at the N-terminus, a subcellular localization of the protein was analyzed after fusing it into the green fluorescent protein (GFP): Both N-term (Jpk-EGFP) and C-term tagged-Jpk (EGFP-Jpk) showed to be localized in the ER when analyzed under the fluorescence microscopy after staining the cells with ER- and MitoTracker. Since ER stress triggers the ER-stress mediated apoptosis to eliminate the damaged cells, we analyzed the expression pattern of Jpk under ER-stress condition. When MCF7 cells were treated with the ER-stress inducer such as DTT and EGTA, the expression of Jpk was upregulated at the transcriptional level like that of Grp78, a molecular chaperone well known to be overexpressed under ER-stress condition. In the presence of high concentration of ER-sterss inducer (10 mM), about 70 (DTT) to $95\%$ (EGTA) of cells died stronly expressing ($10\~12$ fold) Jpk. Whereas at the low concentration ($0.001\~1.0\;mM$) of the inducer, the expression of Jpk was increased about 2.5 (EGTA) to 5 fold (DTT), which is rather similar to those of ER chaperone protein Grp78. These results altogether indicate that the ER-stress upregulated the expression of Jpk and the excess stress induces the ER-stress induced apoptosis and the concomitant expression of Jpk.

• 대한의생명과학회지
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• 제12권4호
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• pp.435-438
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• 2006

In eukaryotes, ER stress induces UPR (unfolded protein response) via IRE1 activation which sends a molecular signal for XBP1 mRNA splicing in the cytosol. During this mRNA splicing, 23 nt removed in which contains PstI site and then resulting XBP1 product is not digested with PstI restriction enzyme. In this study, using this XBP1 mRNA splicing mechanism, the effect of heat shock on thyrocytes is studied, because heat shock response in the thyrocytes needs more study to understand thyroid physiology under alternative environments. ER inducible drugs (tunicamycin, DTT, $Ca^{2+}$ ionopore A23187, BFA) induce ER stress in the thyrocytes. From 3 hours after heat shock, ER stress is induced and which is reversible when heat shock is without. While $Ca^{2+}$ ionopore A23187 is reversible from ER stress by washing out the drug, thapsigagin is irreversible. Other ER inducible drugs are not so sensitive to ER stress repairing. XBP1 mRNA splicing in a cell is very available method to detect ER stress. It needs only a small quantity of total RNA and processing also very easy.

• The Korean Journal of Physiology and Pharmacology
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• 제22권5호
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• pp.567-575
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• 2018

Acute kidney injury (AKI), which is defined as a rapid decline of renal function, becomes common and recently recognized to be closely intertwined with chronic kidney diseases. Current treatment for AKI is largely supportive, and endoplasmic reticulum (ER) stress has emerged as a novel mediator of AKI. Since carbon monoxide attenuates ER stress, the objective of the present study aimed to determine the protective effect of carbon monoxide releasing molecule-2 (CORM2) on AKI associated with ER stress. Kidney injury was induced after LPS (15 mg/kg) treatment at 12 to 24 h in C57BL/6J mice. Pretreatment of CORM2 (30 mg/kg) effectively prevented LPS-induced oxidative stress and inflammation during AKI in mice. CORM2 treatment also effectively inhibited LPS-induced ER stress in AKI mice. In order to confirm effect of CO on the pathophysiological role of tubular epithelial cells in AKI, we used mProx24 cells. Pretreatment of CORM2 attenuated LPS-induced ER stress, oxidative stress, and inflammation in mProx24 cells. These data suggest that CO therapy may prevent ER stress-mediated AKI.

• Biomolecules & Therapeutics
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• 제20권3호
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• pp.346-351
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• 2012

Cells show various stress signs when they are challenged with severe physiological problems. Majority of such cellular stresses are conveyed to endoplasmic reticulum (ER) and unfolded protein response (UPR) serves as typical defense mechanism against ER stress. This study investigated an interaction between ER stress agents using macropage cell line Raw 264.7. When activated by lipopolysaccharide (LPS), the cell lines showed typical indicators of ER stress. Along with molecular chaperones, the activation process leads to the production of additional inflammatory mediators. Following activation, the macrophage cell line was further treated with TUN and characterized in terms of chaperone expression and cytokine secretion. When treated with TUN, the activated macrophage cell leads to increased secretion of IL-6 although expression of ER stress markers, GRP94 and GRP78 increased. The secretion of cytokines continued until the addition of BFA which inhibits protein targeting from ER to Golgi. However, secretion of cytokines was ceased upon dual treatments with BFA and TG. This result strongly implies that cells may differently deal with various polypeptides depending on the urgency in cellular function under ER stress. Considering IL-6 is one of the most important signal molecules in macrophage, the molecule might be able to circumvent ER stress and UPR to reach its targeting site.