• Molecules and Cells
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• v.46 no.4
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• pp.191-199
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• 2023

The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to the insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

• BMB Reports
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• v.54 no.5
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• pp.246-252
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• 2021

The Golgi complex plays a central role in protein secretion by regulating cargo sorting and trafficking. As these processes are of functional importance to cell polarity, motility, growth, and division, there is considerable interest in achieving a comprehensive understanding of Golgi complex biology. However, the unique stack structure of this organelle has been a major hurdle to our understanding of how proteins are secreted through the Golgi apparatus. Herein, we summarize available relevant research to gain an understanding of protein secretion via the Golgi complex. This includes the molecular mechanisms of intra-Golgi trafficking and cargo export in the trans-Golgi network. Moreover, we review recent insights on signaling pathways regulated by the Golgi complex and their physiological significance.

• Journal of Life Science
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• v.26 no.4
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• pp.490-495
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• 2016

Brefeldin A (BFA), a lactone antibiotic isolated from the fungus Eupenicillium brefeldianum, inhibits the transport of secreted and membrane proteins from the endoplasmic reticulum (ER) to the Golgi apparatus. BFA disrupts Golgi function, the accumulation of unfolded proteins in ER, and the induction of ER stress. Prolonged ER stress induces apoptosis at least in part through the transcription factor C/EBP (CCAAT/enhancer binding protein) homologous protein (CHOP),which is activated by the unfolded protein response (UPR). In this paper, we demonstrate that BFA-induced endoplasmic reticulum stress leads to different CHOP expression in primary astrocyte cells and C6 glioma cells. BFA induced lower CHOP expression levels in primary astrocyte cells than in C6 glioma cells; however, other ER stress inducers (thapsigargin and tunicamycin) resulted in similar expression patterns in these two cell types. Interestingly, the three different ER stress inducers (BFA, thapsigargin, and tunicamycin) induced similar levels of CHOP mRNA expression in primary astrocyte cells. The ubiquitin-proteasome inhibitor MG132 also markedly up-regulated the BFA-mediated CHOP protein expression in primary astrocyte cells. BFA also induced higher proteasome activity in primary astrocyte cells than in C6 glioma cells. Taken together, our results suggest that higher proteasomal activity might down-regulate BFA-induced CHOP expression in primary astrocyte cells.

• 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.17 no.6 s.86
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• pp.847-858
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• 2007

The endoplasmic reticulum (ER) is an important intracellular organelle for folding and maturation of newly synthesized transmembrane and secretory proteins. The ER provides stringent quality control systems to ensure that only correctly folded proteins exit the ER and unfolded or misfolded proteins are retained and ultimately degraded. The ER has evolved stress response both signaling pathways the unfolded protein response (UPR) to cope with the accmulation of unfolded or misfolded proteins and ER overload response (EOR). Accumulating evidence suggests that, in addition to responsibility for protein processing, ER is also an important signaling compartment and a sensor of cellular stress. In this respect, production of bio-functional recombinant-proteins requires efficient functioning of the ER secretory pathway in host cells. This review briefly summarizes our understanding of the ER signaling developed in the recent years to help of the secretion capacities of recombinant cells.

• The Korean Journal of Zoology
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• v.38 no.4
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• pp.570-579
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• 1995

Ultrastructural and histochemical changes of mucous cells In the freshwater and seawater-adapted guppy (Poecflia reticulatus) gills were observed by the light, scanning-and transmisslon~lectron microscopes. The mucous cells were usually located in the epithelium of primary lameilne projected from the gill arch. The rough endoplasmic retIculum and Golgi complex were hIghly developed In immature mucous cells. The mature mucous cells were nearly filled with the mucous granules. In the freshwater guppy, the histochemical properties of the mucous cells were a mixture of the neutral mucin, sialomucin and sulfomucin. When guppy was adapted to the seawater, the content of acid glycoproteins (slalomucln and sulfomucin) was decreased. In addition, the number of mucous cells in the seawater-adapted group was less than a third of those in the freshwater one. These results suggest that the seawater-adapted guppy would react to the changed osmotic stress of the seawater. And also, the environmental change by the increased salt concentraion might lead to reduce the chance of infections.

• Molecules and Cells
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• v.42 no.11
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• pp.783-793
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• 2019

When endoplasmic reticulum (ER) functions are perturbed, the ER induces several signaling pathways called unfolded protein response to reestablish ER homeostasis through three ER transmembrane proteins: inositol-requiring enzyme 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Although it is important to measure the activity of ATF6 that can indicate the status of the ER, no specific cell-based reporter assay is currently available. Here, we report a new cell-based method for monitoring ER stress based on the cleavage of $ATF6{\alpha}$ by sequential actions of proteases at the Golgi apparatus during ER stress. A new expressing vector was constructed by using fusion gene of GAL4 DNA binding domain (GAL4DBD) and activation domain derived from herpes simplex virus VP16 protein (VP16AD) followed by a human $ATF6{\alpha}$ N-terminal deletion variant. During ER stress, the GAL4DBD-VP16AD(GV)-$hATF6{\alpha}$ deletion variant was cleaved to liberate active transcription activator encompassing GV-$hATF6{\alpha}$ fragment which could translocate into the nucleus. The translocated GV-$hATF6{\alpha}$ fragment strongly induced the expression of firefly luciferase in HeLa Luciferase Reporter cell line containing a stably integrated 5X GAL4 site-luciferase gene. The established double stable reporter cell line HLR-GV-$hATF6{\alpha}$(333) represents an innovative tool to investigate regulated intramembrane proteolysis of $ATF6{\alpha}$. It can substitute active pATF6(N) binding motif-based reporter cell lines.

• Korean Journal of Acupuncture
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• v.29 no.2
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• pp.260-270
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• 2012

Objectives : Hippocampus, a region of temporal lobe, plays an important role in the pathogenic mechanisms of brain diseases such as Alzheimer's disease, depression and temporal lobe epilepsy. This research is designed to investigate hippocampal changes after acupuncture stimulation at Shinmun(HT7) using 2-dimensional gel electrophoresis(2-DE). Methods : On postnatal-day 15, rat pups were randomly devided into Normal(NOR) or HT7 group. All of Pups kept with their mothers for 7 days, but pups in HT7 group received acupuncture stimulation at HT7 daily. On postnatal-day 21, hippocampus of each rat pup was dissceted 30 minutes after last acupuncture stimulation and the protein expressions were investigated using 2-DE. Results : After acupuncture stimulation at HT7, expression of 20 proteins were significantly increased. Succinate semialdehyde dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase-like, transketolase, aconitate hydratase and phosphoglucomutase-1 were related to glucose methabolism. Eukaryotic initiation factor(eIF) 4A-II, eIF 4A-III, mitochondrial Tu translation elongation factor and chain A of crystal structure of the 70-Kda heat shock cognate protein involve in the protein synthesis in ribosome. Tubulin ${\beta}$-4 chain, tubulin T ${\beta}$-15 and tubulin ${\alpha}$-1B chain comprise cytoskeleton. Glutathione S-transferase(GST) ${\omega}$-1, GST P and GST Yb-3 can reduce oxidative stress. ${\beta}$-soluble N-ethylmaleimide-sensitive fusion protein attachment protein is required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus, glycerol-3-phosphate dehydrogenase plays a major role in lipid biosynthesis, creatine kinase U-type catalyses the conversion of creatine and consumes adenosine triphosphate to create phosphocreatine and adenosine diphosphate. Platelet-activating factor acetylhydrolase IB subunit alpha and voltage depedent anion-selective channel protein 2 were also increased. Conclusions : The results suggest that acupuncture stimulation at HT7 may enhance glucose and lipid metabolism, protein synthesis, cytoskeletal substance and anti-oxidative stress in hippocampus.

• Journal of Life Science
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• v.19 no.8
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• pp.1159-1163
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• 2009

It has been postulated that endoplasmic (ER) stress is involved in the development of several diseases. However, the detailed molecular mechanisms have not been fully understood. Therefore, we characterized a genetic network of genes induced by ER stress using cDNA microarray and gene set expression coherence analysis (GSECA), and identified gene function as well as several transcription regulators associated with ER stress. We analyzed time-dependent gene expression profiles in thapsigargin-treated Sk-Hep1 using an oligonucleotide expression chip, and then selected functional gene sets with significantly high expression coherence which was processed into functional clusters according to the expression similarities. The functions related to sugar binding, lysosome, ribosomal protein, ER lumen, and ER to golgi transport increased, whereas the functions with mRNA processing, DNA replication, DNA repair, cell cycle, electron transport chain and helicase activity decreased. Furthermore, functional clusters were investigated for the enrichment of regulatory motifs using GSECA, and several transcriptional regulators associated with regulation of ER-induced gene expression were found.

• The korean journal of orthodontics
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• v.24 no.2
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• pp.331-348
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• 1994

The purpose of this study was to investigate changes in the shape and ultrastructure of the articular disc of the rat mandibular joint with aging. Mechanical stress applied to the articular disc changes during neonatal, suckling, juvenile, adult and senile stages. Mandibular joints of 6 groups of rats(1-, 7-, 17-, 27-, 55-day and over-1-year groups) were removed en bloc and processed for light and electro microscopic study. The changes in the shape of articular disc were examined by light microscope in each group. Structural and ultrastructural changes in the articular disc were examined by light and electron microscope in each group. The results were as follows : In the 1-day and 7-day groups, the articular disc was long and slender in shape and the articular disc was not fitted with the shape of the mandibular fossa and condyle. However' after that time, the anterior and posterior portions of the articular disc were more bulged and the middle portion was shorter and biconcave. Thus the articular disc was well fitted with the shape of the mandibular fossa and condyle. The cell density decreased with aging. In the l -day and 7-day groups, the Golgi apparatus, rough endoplasmic reticulum and free ribosome, which are involved in the synthesis of intracellular and extracellular matrix, were developed. In the 17-day, 27-day and 55-day groups, not only the cell organelles involved in the synthesis of the intracellular and extracellular matrix but also the cell organelles involved in the remodeling of the extracellular matrix(i.e., finger-like cell process, lysosome and mitochondria)were well developed. With advancing age, intracytoplasmic microfilaments were more accumulated and condroid cells increased. In the over-1-year group, the majority of cells of the articular disc were chondroid cells. The majority of cytoplasmic compartment were filled with intracytoplasmic microfilaments and cell organelles were not developed. Therefore, metabolic activities of the cell was markedly reduced and cells contained structures enduring mechanical stress, and cells which were in the process of degeneration were observed occasionally.