• Journal of Breast Cancer
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• 제21권4호
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• pp.354-362
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• 2018

Cellular stress severely disrupts endoplasmic reticulum (ER) function, leading to the abnormal accumulation of unfolded or misfolded proteins in the ER and subsequent development of endoplasmic reticulum stress (ERS). To accommodate the occurrence of ERS, cells have evolved a highly conserved, selfprotecting signal transduction pathway called the unfolded protein response. Notably, ERS signaling is involved in the development of a variety of diseases and is closely related to tumor development, particularly in breast cancer. This review discusses recent research regarding associations between ERS and tumor metastasis. The information presented here will help researchers elucidate the precise mechanisms underlying ERS-mediated tumor metastasis and provide new directions for tumor therapies.

• 대한의생명과학회지
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• 제13권2호
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• pp.157-160
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• 2007

Endoplasmic reticulum (ER) plays formation of disulfide bonds and proper folding of secretory proteins. Cellular responses to ER stress enhances the stress-activated kinase pathway and the induces a lot of immediate-early genes. Among of them, the early growth response-1 (Egr-1), a transcription factor, which plays an important role in cell growth, development, differentiation, apoptosis and various types of injury. For that reason, we have tested the expression of Egr-1 against ER stress inducible drugs (tunicamycin, DTT, A23187 and BFA) to understand what kind of aspect occurred by ER stresses.

• Molecules and Cells
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• 제44권8호
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• pp.569-579
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• 2021

Cyclase-associated protein 2 (CAP2) has been addressed as a candidate biomarker in various cancer types. Previously, we have shown that CAP2 is expressed during multi-step hepatocarcinogenesis; however, its underlying mechanisms in liver cancer cells are not fully elucidated yet. Here, we demonstrated that endoplasmic reticulum (ER) stress induced CAP2 expression, and which promoted migration and invasion of liver cancer cells. We also found that the ER stress-induced CAP2 expression is mediated through activation of protein kinase C epsilon (PKCε) and the promotor binding of activating transcription factor 2 (ATF2). In addition, we further demonstrated that CAP2 expression promoted epithelial-mesenchymal transition (EMT) through activation of Rac1 and ERK. In conclusion, we suggest that ER stress induces CAP2 expression promoting EMT in liver cancer cells. Our results shed light on the novel functions of CAP2 in the metastatic process of liver cancer cells.

• 생명과학회지
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• 제22권8호
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• pp.1132-1136
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• 2012

많은 종류의 세포스트레스는 unfolded protein response (UPR)관련인자의 유전자발현을 조절한다. 본 연구결과 부동스트레스(immobilization stress)는 세포의 소포체스트레스(ER stress)와 관련된 유전자발현의 변화를 유도한다; Heart, spleen, thymus, kidney, testis에서는 유전자발현 변화가 없었지만 adrenal gland, liver, lung에서는 유의할만한 상승변화가 있었다. 그러나 muscle에서는 다른 것들과 대조적으로 발현이 감소되었다. 이 결과는 부동스트레스도 다른 종류의 세포스트레스와 같이 세포수준에서 UPR을 조절할 수 있다는 최초의 보고이다.

• 대한의생명과학회지
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• 제11권2호
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• pp.249-252
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• 2005

The mammalian unfolded protein response (UPR) protects the cell. against the stress of unfolded or misfolded proteins in the endoplasmic reticulum (ER). It has recently demonstrated that IRE1, PERK, ATF6, and X-box protein 1 (XBP-l) directly or indirectly participate in this process. Upon accumulation of unfolded/misfolded proteins in the ER lumen, release of BiP from Ire1p permits dimerization and autophosphorylation to activate its kinase and endoribonulease activities to initiate XBP-1 mRNA splicing. Spliced XBP-1 mRNA removed middle part of 23 bp and encodes a potent transcription factor, XBP-l protein that binds to the unfolded protein response element (UPRE) or endoplasmic reticulum stress element (ERSE) sequence of many UPR target genes and produces several kind of ER chaperones. In this study, we described both the result and the detailed experimental procedures of XBP-1 mRNA splicing induced by ER stress, this result might help to elucidate the roles of the UPR and early diagnosis in a number of human diseases involving endoplasmic reticulum storage disease (ERSD).

• 운동영양학회지
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• 제17권2호
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• pp.35-42
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• 2013

The purpose of this study was to identify the effects of gene expression of endoplasmic reticulum (ER) stress in skeletal muscle and adipose tissue on acute exhaustive exercise. Thirty-five Sparague Dawley male rats were divided into a control group (CON, n = 7) and a exhaustive exercise group (n = 28), immediately after exhaustive exercise group (n = 7), after 30 minutes exhaustive exercise group (n = 7), after 60 minutes exhaustive exercise group (n = 7), after 180 minutes exhaustive exercise group (n = 7). As a result, changes in the composition of the blood serum triglyceride concentration increased significantly in immediately after exhaustive exercise group, On the contrary, blood glucose showed a significantly decreased (p < .05). Homeostasis of energy metabolism due to exhaustive exercise as a result of the mechanism of action of skeletal muscle in the glycogenolysis and absorption, which indicates that the process of means. On the other hand, a result of examining changes in endoplasmic reticulum stress-related proteins in skeletal muscle and adipose tissue, JNK1 except in skeletal muscle BiP, ATF4, CHOP, GRP78 mRNA increased significantly immediately after exercise, and after 30 minutes returned to normal levels that could be confirmed (p < .05). BiP mRNA in adipose tissue show a similar pattern and skeletal muscle increased significantly immediately after exercise, but other changes in the specificity of the endoplasmic reticulum stress-related proteins also did not appear. In conclusion, Exercise applies and exercise training duration and exercise intensity as well as research on the interaction of the endoplasmic reticulum stress-related genes should be study continuously, to be more clear.

• Journal of Nutrition and Health
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• 제52권2호
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• pp.176-184
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• 2019

Purpose: Protein overloading in the endoplasmic reticulum (ER) leads to endoplasmic reticulum stress, which exacerbates various disease conditions. Emodin, an anthraquinone compound, is known to have several health benefits. The effect of emodin against palmitic acid (PA) - induced ER stress in HepG2 cells was investigated. Methods: HepG2 cells were treated with varying concentrations of palmitic acid to determine the working concentration that induced ER stress. ER stress associated genes such as ATF4, XBP1s, CHOP and GRP78 were checked using RT- PCR. In addition, the expression levels of unfolded protein response (UPR) associated proteins such as $IRE1{\alpha}$, $eIF2{\alpha}$ and CHOP were checked using immunoblotting to confirm the induction of ER stress. The effect of emodin on ER stress was analyzed by treating HepG2 cells with $750{\mu}M$ palmitic acid and varying concentrations of emodin, then analyzing the expression of UPR associated genes. Results: It was evident from the mRNA and protein expression results that palmitic acid significantly increased the expression of UPR associated genes and thereby induced ER stress. Subsequent treatment with emodin reduced the mRNA expression of ATF4, GRP78, and XBP1s. Furthermore, the protein levels of $p-IRE1{\alpha}$, $p-eIF2{\alpha}$ and CHOP were also reduced by the treatment of emodin. Analysis of sirtuin mRNA expression showed that emodin increased the levels of SIRT4 and SIRT7, indicating a possible role in decreasing the expression of UPR-related genes. Conclusion: Altogether, the results suggest that emodin could exert a protective effect against fatty acid-induced ER stress and could be an agent for the management of various ER stress related diseases.

• 한국발생생물학회지:발생과생식
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• 제25권1호
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• pp.43-53
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• 2021

We examine the effect of endoplasmic reticulum (ER) stress inhibitor treatment time on the in vitro development of porcine somatic cell nuclear transfer (SCNT) embryos. Porcine SCNT embryos were classified by four groups following treatment time of ER stress inhibitor, tauroursodeoxycholic acid (TUDCA; 100 µM); 1) non-treatment group (control), 2) treatment during micromanipulation process and for 3 h after fusion (NT+3 h group), 3) treatment only during in vitro culture after fusion (IVC group), and 4) treatment during micromanipulation process and in vitro culture (NT+IVC group). SCNT embryos were cultured for six days to examine the X-box binding protein 1 (Xbp1) splicing levels, the expression levels of ER stress-associated genes, oxidative stress-related genes, and apoptosis-related genes in blastocysts, and in vitro development. There was no significant difference in Xbp1 splicing level among all groups. Reduced expression of some ER stress-associated genes was observed in the treatment groups. The oxidative stress and apoptosis-related genes were significantly lower in all treatment groups than control (p<0.05). Although blastocyst development rates were not different among all groups (17.5% to 21.7%), the average cell number in blastocysts increased significantly in NT+3 h (48.5±2.3) and NT+IVC (47.7±2.4) groups compared to those of control and IVC groups (p<0.05). The result of this study suggests that the treatment of ER stress inhibitor on SCNT embryos from the micromanipulation process can improve the reprogramming efficiency of SCNT embryos by inhibiting the ER and oxidative stresses that may occur early in the SCNT process.

• Molecules and Cells
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• 제38권10호
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• pp.851-858
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• 2015

Disturbed blood flow with low-oscillatory shear stress (OSS) is a predominant atherogenic factor leading to dysfunctional endothelial cells (ECs). Recently, it was found that disturbed flow can directly induce endoplasmic reticulum (ER) stress in ECs, thereby playing a critical role in the development and progression of atherosclerosis. Ursodeoxycholic acid (UDCA), a naturally occurring bile acid, has long been used to treat chronic cholestatic liver disease and is known to alleviate endoplasmic reticulum (ER) stress at the cellular level. However, its role in atherosclerosis remains unexplored. In this study, we demonstrated the anti-atherogenic activity of UDCA via inhibition of disturbed flow-induced ER stress in atherosclerosis. UDCA effectively reduced ER stress, resulting in a reduction in expression of X-box binding protein-1 (XBP-1) and CEBP-homologous protein (CHOP) in ECs. UDCA also inhibits the disturbed flow-induced inflammatory responses such as increases in adhesion molecules, monocyte adhesion to ECs, and apoptosis of ECs. In a mouse model of disturbed flow-induced atherosclerosis, UDCA inhibits atheromatous plaque formation through the alleviation of ER stress and a decrease in adhesion molecules. Taken together, our results revealed that UDCA exerts anti-atherogenic activity in disturbed flow-induced atherosclerosis by inhibiting ER stress and the inflammatory response. This study suggests that UDCA may be a therapeutic agent for prevention or treatment of atherosclerosis.

• Clinical and Experimental Reproductive Medicine
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• 제42권1호
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• pp.1-7
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• 2015

Stress coping mechanisms are critical to minimize or overcome damage caused by ever changing environmental conditions. They are designed to promote cell survival. The unfolded protein response (UPR) pathway is mobilized in response to the accumulation of unfolded proteins, ultimately in order to regain endoplasmic reticulum (ER) homeostasis. Various elements of coping responses to ER stress including Perk, Ask1, Bip, Chop, Gadd34, Ire1, Atf4, Atf6, and Xbp1 have been identified and were found to be inducible in oocytes and preimplantation embryos, suggesting that, as a normal part of the cellular adaptive mechanism, these coping responses, including the UPR, play a pivotal role in the development of preimplantation embryos. As such, the UPR-associated molecules and pathways may become useful markers for the potential diagnosis of stress conditions for preimplantation embryos. After implantation, ER stress-induced coping responses become physiologically important for a normal decidual response, placentation, and early organogenesis. Attenuation of ER stress coping responses by tauroursodeoxycholate and salubrinal was effective for prevention of cell death of cultured embryos. Further elucidation of new and relevant ER stress coping responses in periimplantation embryos might contribute to a comprehensive understanding of the regulation of normal development of embryonic development and potentiation of embryonic development in vitro.