• BMB Reports
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• 제45권8호
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• pp.482-487
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• 2012

To identify the novel inhibitors of endoplasmic reticulum stress-induced cell death, we performed a high throughput assay with a chemical library containing a total of 3,280 bioactive small molecules. Cyclosporine A and bromocriptine were identified as potent inhibitors of thapsigargiin-induced cell death (cut-off at $4{\sigma}$ standard score). However, U74389G, the potent inhibitor of lipid peroxidation had lower activity in inhibiting cell death. The inhibition effect of cyclosporine A and bromocriptine was specific for only thapsigargin-induced cell death. The mechanism of inhibition by these compounds was identified as modification of the expression of glucose regulated protein-78 (GRP-78/Bip) and inhibition of phosphorylation of p38 mitogen activated protein kinase (MAPK). However, these compounds did not inhibit the same events triggered by tunicamycin, which was in agreement with the cell survival data. We suggest that the induction of protective unfolded protein response by these compounds confers resistance to cell death. In summary, we identified compounds that may provide insights on cell death mechanisms stimulated by ER stress.

• BMB Reports
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• 제42권11호
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• pp.719-724
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• 2009

Recent studies have revealed that endoplasmic reticulum (ER) disturbance is involved in the pathophysiology of neurodegenerative disorders, contributing to the activation of the ER stress-mediated apoptotic pathway. Therefore, we investigated here the molecular mechanisms underlying the ER-mitochondria axis, focusing on calcium as a potential mediator of cell death signals. Using NT2 cells treated with brefeldin A or tunicamycin, we observed that ER stress induces changes in the mitochondrial function, impairing mitochondrial membrane potential and distressing mitochondrial respiratory chain complex Moreover, stress stimuli at ER level evoked calcium fluxes between ER and mitochondria. Under these conditions, ER stress activated the unfolded protein response by an overexpression of GRP78, and also caspase-4 and-2, both involved upstream of caspase-9. Our findings show that ER and mitochondria interconnection plays a prominent role in the induction of neuronal cell death under particular stress circumstances.

• Applied Microscopy
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• 제20권2호
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• pp.71-80
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• 1990

It was investigated the morphological changes of differentiating epidermal cells in chick embryos. Ectodermal cells at 3 days after incubation were cuboidal, their nuclei were large, and rough endoplasmic reticulum and mitochondria were distributed in the cytoplasm. At 5 days after incubation, there were periderm and one basal layer in epidermis. The cells of basal layer were columnar, their nuclei were round, and rough endoplasmic reticulum and free ribosomes were developed. Also, peridermal cells were flat, chromatins were partially condensed and glycogen particles were abundant. No periderm showed and cells of basal layer formed intermediate layer at 9 days after incubation. Basal cells of intermediate layer were cuboidal, neighboring cells were anchored by desmosomes and tonofibrils and free ribosomes were evenly scattered. At 15 days after incubation, stratum corneum and stratum germinativum were distinguished. In cells of stratum germinativum, tonofibrils, free ribosomes and desmosomes were well developed. And then, the shedding of stratum corneum were showed at 17 days after incubation and stratum corneum were well developed after hatching.

• Applied Microscopy
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• 제8권1호
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• pp.67-76
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• 1978

A comparative investigation of fine structure of callus cells derived from tissue culture of Panax ginseng was made by electron microscope. Callus was consisted of large superficial cells and small inner zone cells derived from shoot apex tissue cultured for 16 weeks. Large superficial cells were contained the clusters of starch grains surrounded by a double plastid membrane. Especially, electron dense particles were deposited just inside and outside of plastid membrane and also deposited on mitochondria-like and endoplasmic reticulum-like structures. Crystalline body was also found in superficial cells. Small inner zone cells were characterized by presence of proplastids sheathed by short endoplasmic reticulum profiles. presence of spiral configuration of ribosomes and absence of crystalline body. Organ primordia was consisted of a dense cytoplasm and notable nucleate cells derived from nodal tissue cultured for 67 weeks. Proplastids containing starch grains and crystalline bodies were frequently observed; starch grains are of small quantity and does not form the clusters as in inner zone cells; hexagonal crystalline body itself does not have always limiting membrane. Remarkably. in a few cells of primordia, particles resembling the presumptive virus were observed mainly in condensed nuclear chromatin and also in cytoplasm, in mitochondrion-like organelle.

• Applied Microscopy
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• 제26권2호
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• pp.197-206
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• 1996

cis-Dichlorodiammineplatinum (II) (cis-Platin) inhibits the proliferation and growth of the tumor cells by way of inhibiting DNA and protein synthesis of the cancer cells. Although cis-Platin is very effective antitumor drug, it also produces many other side effects. Thus the author has studied the effects of cis-Platin on the proximal epiphyseal plate in the tibia of the rat. The results were as follows: In the chondrocyte of the proliferative zone, sacculated, and fragmented cisternae of rough endoplasmic reticulum, some mitochondria with disorganized mitochondrial cristae and distorted procollagens were observed, and in the matrix some large matrix granules and dispersed collagen fibrils were revealed on the 1st, 3rd day and 1st week group of cis-Platin treated rats. In the chondrocyte of the proliferative zone of cis-Platin treated rats on the 2nd and 3rd week group, parallely arranged rough endoplasmic reticulum and many procollagens were shown, and in the matrix a number of large matrix granules and many small matrical granules as well as collagen fibrils were revealed. Consequently it is suggested that though cis-Platin induces the degenerative changes of the chondrocyte resulting in components of the cartilagenous matrix, these toxic effects are regressed with time.

• 미생물학회지
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• 제22권1호
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• pp.19-28
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• 1984

A. conoides에 의한 선충 포획과정을 SEM과 TEM을 이용하여 관찰하였다. 1. A. conoides는 점착성 three-dimensional networks에 의해 선충을 포획한다. 2. Trap cell은 영양균사에 비해 세포벽이 두꺼우며 endoplasmic reticulum, mitochondria 및 electron-dense granule이 풍부하다. 3. 포획기관에서만 관찰되는 전자밀도가 높은 과립은 포획기관이 선충을 점착하여 침투하는 과정에서 소실된다. 4. 포획기관과 선충이 부착된 사이에서 osmiophilic layer가 관찰되었고 바로 이 지점으로부터 침투가 일어나며, 한 포획기관에서 두 군데 이상 동시 침투가 가능하다. 5. 포획기관의 선충내 침투시 appressorium이 형성되지 않고 침투되는 경우가 있다. 6. 균주와 선충의 혼합배지를 2~3주 두었을 때, 유충들이 포자에 접착되어 죽는다.

• BMB Reports
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• 제48권8호
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• pp.445-453
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• 2015

Endoplasmic Reticulum (ER) is an organelle where most secretory and membrane proteins are synthesized, folded, and undergo further maturation. As numerous conditions can perturb such ER function, eukaryotic cells are equipped with responsive signaling pathways, widely referred to as the Unfolded Protein Response (UPR). Chronic conditions of ER stress that cannot be fully resolved by UPR, or conditions that impair UPR signaling itself, are associated with many metabolic and degenerative diseases. In recent years, Drosophila has been actively employed to study such connections between UPR and disease. Notably, the UPR pathways are largely conserved between Drosophila and humans, and the mediating genes are essential for development in both organisms, indicating their requirement to resolve inherent stress. By now, many Drosophila mutations are known to impose stress in the ER, and a number of these appear similar to those that underlie human diseases. In addition, studies have employed the strategy of overexpressing human mutations in Drosophila tissues to perform genetic modifier screens. The fact that the basic UPR pathways are conserved, together with the availability of many human disease models in this organism, makes Drosophila a powerful tool for studying human disease mechanisms. [BMB Reports 2015; 48(8): 445-453]

• BMB Reports
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• 제47권10호
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• pp.563-568
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• 2014

Human genome projects have enabled whole genome mapping and improved our understanding of the genes in humans. However, many unknown genes remain to be functionally characterized. In this study, we characterized human chromosome 4 open reading frame 34 gene (hC4orf34). hC4orf34 was highly conserved from invertebrate to mammalian cells and ubiquitously expressed in the organs of mice, including the heart and brain. Interestingly, hC4orf34 is a novel ER-resident, type I transmembrane protein. Mutant analysis showed that the transmembrane domain (TMD) of hC4orf34 was involved in ER retention. Overall, our results indicate that hC4orf34 is an ER-resident type I transmembrane protein, and might play a role in ER functions including $Ca^{2+}$ homeostasis and ER stress.

• 대한의생명과학회지
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• 제16권4호
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• pp.359-363
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• 2010

The miniature pig is a very suitable donor species in xenotransplantation of human organs. Intestine ischemia/reperfusion (I/R) is associated with high morbidity and mortality. Endoplasmic reticulum (ER) stress and apoptosis has been associated with the onset of diverse diseases. Thus, we examined the effect of intestine I/R on the expression of ER stress and apotptosis related molecules. In the present study, I/R induced phosphorylation of protein kinase-like endoplasmic reticulum kinase (PERK), IRE, and ATF-4. I/R also increased the expression of the proapoptotic transcription factor CAAT/enhancer-binding protein homologous protein (CHOP). In addition, I/R decreased the expression of Bcl-2, but increased the expression of Bax, cleaved PARP, and cleaved caspase-3. Moreover, I/R increased splicing form of XBP-1 mRNA and the expression of caspase-6 and caspase-3 mRNA. In conclusion, intestine I/R induced ER stress and apoptosis in miniature pig.

• BMB Reports
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• 제45권5호
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• pp.317-322
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• 2012

2-deoxy-D-glucose(2DG)-caused endoplasmic reticulum (ER) stress inhibits protein phosphorylation at tyrosine residues. However, the accurate regulatory mechanisms, which determine the inflammatory response of chondrocytes to ER stress via protein tyrosine phosphorylation, have not been systematically evaluated. Thus, in this study, we examined whether protein phosphorylation at tyrosine residues can modulate the expression and glycosylation of COX-2, which is reduced by 2DG-induced ER stress. We observed that protein tyrosine phosphatase (PTP) inhibitors, sodium orthovanadate (SOV), and phenylarsine oxide (PAO) significantly decreased expression of ER stress inducible proteins, glucose-regulated protein 94 (GRP94), and CCAAT/ enhancer-binding-protein- related gene (GADD153), which was induced by 2DG. In addition, we demonstrated that SOV and PAO noticeably restored the expression and glycosylation of COX-2 after treatment with 2DG. These results suggest that protein phosphorylation of tyrosine residues plays an important role in the regulation of expression and glycosylation during 2DG-induced ER stress in rabbit articular chondrocytes.