• BMB Reports
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• v.32 no.3
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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.

• Biomedical Science Letters
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• v.14 no.1
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• pp.59-62
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• 2008

This experiment was performed to study the effect of TSH (thyroid-stimulating hormone) on the expression of endoplasmic reticulum (ER) chaperones in the rat thyrocytes FRTL-5 cells. Although the expressions of ER membrane kinases (ATF6, IRE1 and PERK) were specially enhanced under absence of TSH, no remarkable up- or down regulations of ER chaperones (BiP, CHOP and Calnexin) were detected by TSH. We firstly report here that TSH by dose up-regulated expression of ER membrane kinases in FRTL-5 culture thyrocytes.

• Biomedical Science Letters
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• v.11 no.2
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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).

• Journal of Life Science
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• v.12 no.2
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• pp.53-56
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• 2002

The baculovirus expression vector system (BEVS) is one of the powerful heterologous protein expression systems using insect cells. As a result this has become a hot issue in the fleld of biotechnology. The advantage of the BEVS is that the large-scale production of heterologous proteins, which undergo posttranslational modification in the endoplasmic reticulum (ER), can be accomplished. Altrough posttranslational modification of heterologous proteins in insect cells is more similar to mammalian cells than yeast, it is not always identical. Therefore, aggregation and degradation can sometimes occur in the ER. To produce a high level of bioactive heterologous proteins using BEVS in insect cells, the prerequisite is to completely understand the posttranslational conditions that determine how newly synthesized polypeptides are folded and assembling with ER chaperones in the ER lumen. Here, we provide information on current BEVS problems and the possibility of successful heterologous protein production from mammalian cells.

• Journal of Life Science
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• v.22 no.8
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• pp.1132-1136
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• 2012

Many kind of cell stresses induce gene expression of unfolded protein response (UPR)-associated factors. This study demonstrated that up- and down-regulation of gene expression of endoplasmic reticulum (ER) stress chaperones and ER stress sensors was induced by immobilization stress in the rat organs (adrenal gland, liver, lung, muscle). However, no statistically significant regulation was detected in the others (heart, spleen, thymus, kidney, testis). The results are the first to show that immobilization stress induces UPR associated gene expression, will help to explain immobilization stress-associated ER stress.

• Journal of Life Science
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• v.23 no.9
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• pp.1104-1108
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• 2013

Ethylene glycol (EG) is the most commonly used for automotive antifreeze, and it's easily misuseful for human. EG poisoning occurs in suicide attempts and infrequently, either intentionally through misuse or accidentally because of sweet taste. Though EG itself is mild toxic to the human body, it becomes higher toxic organic acids by in vivo broken down that are responsible for extensive cellular damage in various tissues caused principally by the metabolites. It is already well known that various cellular stresses induce gene expression of endoplasmic reticulum (ER) chaperones and ER stress sensors. This study demonstrated that regulation of gene expression of ER chaperones and ER stress sensors was induced by EG in rat tissues, and in tissues histological changes are also detected by both staining H&E and immunofluorescent.

• Biomolecules & Therapeutics
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• v.20 no.3
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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.

• 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.

• Molecules and Cells
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• v.38 no.2
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• pp.145-150
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• 2015

Continuous intra- and extracellular stresses induce disorder of $Ca^{2+}$ homeostasis and accumulation of unfolded protein in the endoplasmic reticulum (ER), which results in ER stress. Severe long-term ER stress triggers apoptosis signaling pathways, resulting in cell death. Neural epidermal growth factor-like like protein 2 (NELL2) has been reported to be important in protection of cells from cell death-inducing environments. In this study, we investigated the cytoprotective effect of NELL2 in the context of ER stress induced by thapsigargin, a strong ER stress inducer, in Cos7 cells. Overexpression of NELL2 prevented ER stress-mediated apoptosis by decreasing expression of ER stress-induced C/EBP homologous protein (CHOP) and increasing ER chaperones. In this context, expression of anti-apoptotic Bcl-xL was increased by NELL2, whereas NELL2 decreased expression of pro-apoptotic proteins, such as cleaved caspases 3 and 7. This anti-apoptotic effect of NELL2 is likely mediated by extracellular signal-regulated kinase (ERK) signaling, because its inhibitor, U0126, inhibited effects of NELL2 on the expression of anti- and pro-apoptotic proteins and on the protection from ER stress-induced cell death.

• The Plant Pathology Journal
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• v.31 no.4
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• pp.323-333
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• 2015

As sessile organisms, plants are exposed to persistently changing stresses and have to be able to interpret and respond to them. The stresses, drought, salinity, chemicals, cold and hot temperatures, and various pathogen attacks have interconnected effects on plants, resulting in the disruption of protein homeostasis. Maintenance of proteins in their functional native conformations and preventing aggregation of non-native proteins are important for cell survival under stress. Heat shock proteins (HSPs) functioning as molecular chaperones are the key components responsible for protein folding, assembly, translocation, and degradation under stress conditions and in many normal cellular processes. Plants respond to pathogen invasion using two different innate immune responses mediated by pattern recognition receptors (PRRs) or resistance (R) proteins. HSPs play an indispensable role as molecular chaperones in the quality control of plasma membrane-resident PRRs and intracellular R proteins against potential invaders. Here, we specifically discuss the functional involvement of cytosolic and endoplasmic reticulum (ER) HSPs/chaperones in plant immunity to obtain an integrated understanding of the immune responses in plant cells.