• 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.

• 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.

• International Journal of Industrial Entomology and Biomaterials
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• 제37권1호
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• pp.15-20
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• 2018

Most proteins produced in the endoplasmic reticulum (ER) of eukaryotic cells fold via disulfide formation (oxidative folding). Oxidative folding is catalyzed by protein disulfide isomerase (PDI) and PDI-related ER protein thiol disulfide oxidoreductases (ER oxidoreductases). In yeast and mammals, ER oxidoreductin-1s (ERO1s) supply oxidizing equivalent to the active centers of PDI. We previously identified and characterized the ERO1 of Bombyx mori (bERO1) as a thioredoxin-like protein that shares primary sequence homology with other ERO1s. Here we compare the reactivation of inactivated rRNase and sRNase by bERO1, and show that bERO1 and bPDI cooperatively refold denatured RNase A. This is the first result suggesting that bERO1 plays an essential role in ER quality control through the combined activities of bERO1 and bPDI as a catalyst of protein folding in the ER and sustaining cellular redox homeostasis.

• 한국동물학회지
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• 제11권1호
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• pp.5-12
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• 1968

有尾兩棲類중 Triturus pyrrhogaster에서 人爲的으로 水晶體를 摘出하면, 虹彩의 瞳孔周緣上部中央의 色素上皮가 水晶體로 metaplasia 하는 것은 옛적부터 알려진 事實이다. 이 過程에는 色素上皮의 脫色增殖과 水晶體原基(水晶體胞)의 形成이 보이며 그 後의 水晶體形成은 正常發生의 그것과 全혀 같은 樣相으로 進行한다. 虹彩色素上皮의 細胞가 水晶體의 細胞로 變하는 過程에 대하여서는 벌써 Eguchi, Karasaki 等에 依하여 subcellular level의 解析 報告되었다. Eguchi(1964)의 報告에 依하면 細胞構成要素中 endoplasmic reticulum(ER) 및 mitochondria의 變化가 特히 興味를 끈다. ER 는 脫色이 完了된 細胞에서 核外膜의 泡狀變形에 依하여 形成된 事實로서 觀察되었으며, mitochondria 의 形態 크기 數의 變化도 顯著하였다. 本硏究는 ER 와 mitochondria를 問題의 焦點으로하여 活潑히 伸長되고있는 水晶體纖維細胞中 이 兩者의 細胞構造가 어떤 消長을 나타내는가를 電子顯微鏡으로서 調査한 것이다. 水晶體纖維는 立方狀의 水晶體上皮細胞가 水晶體의 後壁(網膜側)에서 伸長分化한 것인데 ER는 그의 基部 特히 核의 周邊에서만이 顯著한 發達을 나타내고 있었다. 또한 核外膜 은 顯著한 泡狀變化로서 近處의 ER에 連結되어 있었다. 核周邊의 ER는 一般的으로 reticular 構造를 나타내지 않고 큰 cisternae 空間을 가졌다. 그것은 外圍에 있는 粗面構成에 附着시키고 있었다. 一方 小型의 胞狀構造는 細胞質內에 散在 하고있었는데 여기에도 ribosome의 附着이 間或 觀察되는 까닭에 亦是 ER의 一斷面이라고 推定되었다. 纖維細胞의 核에서 먼 伸張端(apical portion)에 있는 ER의 構造는 漸次 沈滯하여 胞狀이 보였다. mitochondria에 對하여서도 ER와 같이 基部核周邊에 發達이 顯著하였다. ER의 周邊에도 密集하여 存在하며 間或 ER의 膜構造와 mitochondria의 外膜이 密接한 것도 觀察되었다. 이와같은 境遇의 ribosome은 polysome狀으로 되어서 緻密하게 散在하여 核의 周邊部에서 水晶體 protein의 合成이 旺盛하게 集行되고 있는 것이라고 推察될만한 微細構造上의 關係를 나타내고 있었다. 纖維의 伸張端近處의 mitochondria는 多少變形되어, 空胞化가 甚하며 때로는 mierin 狀重層膜構造를 連結시키며 大小多數의 胞狀構造와도 共存하고 있었다. 또 細胞間隔에도 이와같은 構造의 樣狀이 認定되는 것도 間或 있었다. 以上 水晶體纖維細胞의 核周邊部에 있어서 ER, mitochondria의 顯著한 發達像은, 核內 RNA 合成의 上昇에서 보이는 polysome의 增加에 뒷받침되는 硏究다. 卽 水晶體蛋白質의 合成에 큰 役割을 나타내는 것이라고 생각된다. 纖維가 伸張하는데 따라서 이들 膜構造는 漸次 細胞의 伸張端에서 退化를 始作하여 消失하는 像을 보이고 있으며 細胞의 退化消失에서도 確認되었다.

• 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.

• BMB Reports
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• 제32권3호
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• pp.311-316
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• 1999

Studies in adipocytes indicate that secretion of active lipoprotein lipase (LPL) was strictly regulated by a quality control system in the endoplasmic reticulum (ER). However, there has been no report about the ER chaperones participating in the folding and assembly of LPL. Many chaperones are known to bind unfolded proteins and dissociate from them through the ATP-hydrolyzing reaction. In this study, putative ER chaperones for LPL were determined by affinity chromatography using denatured LPL as an affinity ligand and elution with ATP. BiP, grp94, calreticulin, and another 50 kDa K-D-E-L protein in the ER of rat adipose tissue were bound to denatured LPL and eluted by ATP. Calnexin was bound to denatured LPL; however, it was not eluted by ATP but by acetic acid. These results indicate that, at least, BiP, grp94, calreticulin, calnexin, and the unidentified 50 kDa protein might act as putative chaperones for the proper folding and assembly of LPL in ER.

• 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.

• 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.

• 대한의생명과학회지
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• 제13권2호
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• pp.153-155
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• 2007

Ferritin heavy chain 1 (FTH1) is an ubiquitous and highly conserved protein which plays a major role in iron homeostasis. The expression of FTH1 was specifically enhanced under various condition of endoplasmic reticulum (ER) stresses drugs such as Brefeldin A (BFA), DTT (Dithiothreitol), calcium ionophore A23187 and tunicamycin. We firstly report here that ER-stress induces up-regulated expression of FTH1 in FRTL-5 culture thyrocytes.

• Journal of Ginseng Research
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• 제15권2호
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• pp.131-138
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• 1991

This study was carried out to investigate the development of endoplasmic reticulum and the formation of Protein body in the endosperm cell during seed formation of Panax ginseng C. A. Meyer with electron microscope. In the endosperm cell of early developmental process after pollination, vesicles that contain storage materials produced in rough endoplasmic reticulum incorporated into central vacuole. The central vacuole is gradually subdivided into several small-sized vacuoles and increased in number. Amorphous proteinaceous materials of high electron density are produced in rough endoplasmic reticulum. Rough endoplasmic reticulum increase in number and surround the protein body and vesicles circularly. Spherical proteinaceous granules with limited membrane appeared from the amorphous granules at the peripheral region of the rough endoplasmic reticulum. Gradually, storage materials are accumulated within the vacuole surrounded by spherosomes. Protein bodies are formed by interfusing between vacuoles and vesicles derived from rough endoplasmic reticulum which contained the amorphous protein of high electron density.