• BMB Reports
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• v.47 no.10
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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.

• Biomedical Science Letters
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• v.16 no.4
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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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• v.45 no.5
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.3
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• pp.287-292
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• 2012

The results of this study intended to clarify the apoptotic effects of curcumin on Epstein-Barr virus transformed human B lymphoma (EBV-B) cells are summarized as follows: It was found that curcumin induced endoplasmic reticulum(ER) stress as well as apoptotic cell death in EBV-B cells, although the magnitude of action was insignificant. When EBV-B cells activated by pokeweed mitogen (PWM) were treated with the same concentrations of curcumin, it was found that higher ER stress (GRP78, P-PERK, XBP-1, ATF6, and CHOP expressed) increased unfold protein response (UPR) and thus, apoptosis attributed to ER stress, compared to non-activated EBV-B cells In conclusion, it is expected that curcumin will play an important role for leukemia treatment.

• Korean Journal of Plant Tissue Culture
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• v.27 no.5
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• pp.375-377
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• 2000

It is now generally accepted that a phosphoinositide cycle is involved in the transduction of a variety of signals in plant cells. In animal cells, the hydrolysis of phosphatidyl-4,5-bisphosphate catalysed by phosphatidylinositol - specific phospholipase C yields to D-myo-inositol - 1,4,5-trisphosphate and diacylglycerol, which are well known second messengers. The binding of InsP$_3$to a receptor located on the endoplasmic reticulum triggers a calcium release from the endoplasmic reticulum. We have detected and partially characterised key components of phosphoinositide signaling. First, tobacco microsomal fraction and plasma membrane PI-PLC. Consecutively, using a radioligand binding assay we have identified a $Ca^{2+}$ -dependent high affinity InsP$_3$binding site in microsomal membrane fraction vesicle preparation and then we have measured inositol-1,4,5-trisphosphate induced calcium release from tobacco microsomal fraction. These findings suggest that phosphoinositide signaling system is present and operates in the tobacco suspension culture.e.

• 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.

• Applied Microscopy
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• v.17 no.1
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• pp.169-176
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• 1987

Naturally occurring canine transmissible venereal tumors of genital organs in mature and regressive stages from 6 dogs were examined by transmission electron microscope. The tumor cells at the stage of maturation were comprised of large round and ovoid cells with prominent nuclei and nucleoli, a few spindle-shaped cells, and irregularly shaped cells. The mature round cells were characterized by the presence of a central ovoid to irregularly round nucleus with a large eccentric nucleolus, vesicular endoplasmic reticulum, round to oval swollen mitochondria with few cristae, Golgi's apparatus, and plasma membranes with numerous microvilli. As the tumor degenerated, the tumor cells were increased in the number of spindle-shaped, fibroblast-like and irregularly shaped cells, collagen bundles, and mainly lymphocytes, in contrast to those of the stage of maturation. Regressing tumor cells were characterized by the swelling and vacuolation of mitochondria and endoplasmic reticulum, membrane-bound granules, lamellar complex, tubular structures, and dense bundles of collagen. It was suggested that transformation might occur in the course of tumor growth causing morphological change from the round to the fibroblast-like cells, and that there was the evidence of cell-mediated tumor cell lysis by lymphocyte infiltration.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.240-244
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• 2007

Cigarette smoking causes serious health problems in humans, especially if smoking habits are established during their adolescence. Nicotine is known to mutate DNA and interfere with apoptosis. Apoptosis is considered as a potent defense mechanism against cellular damaging agents. This study aims to investigate the effect of nicotine on the progression of apoptosis induced under ER stress conditions using four different established cell lines: HEK293, 3T3-L1, C2C12, and HepG2. When treated with nicotine, the progression of apoptosis was notably inhibited in the four cell lines according to the assays of caspase-3 activation and DNA fragmentation. In ER-stressed cells, nicotine appears to inhibit the progression of apoptosis in a concentration-dependent manner. When cells were treated with nicotine prior to ER stress, GRP94 level significantly increased compared to other ER stress markers of PDI and GRP78. This observation suggests that the inhibitory effect of nicotine may results from up-regulation of GRP94, an anti-apoptotic chaperone, under nicotine treatment. Taken together, the present study strongly implies that nicotine may inhibit apoptosis, caused by prolonged ER stress, based on promotion of GRP94 expression.

• BMB Reports
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• v.50 no.3
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• pp.144-149
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• 2017

Ceramides are the major sphingolipid metabolites involved in cell survival and apoptosis. When HepG2 hepatoma cells were treated with celecoxib, the expression of the genes in de novo sphingolipid biosynthesis and sphingomyelinase pathway was upregulated and cellular ceramide was elevated. In addition, celecoxib induced endoplasmic reticulum (ER) stress in a time-dependent manner. SPTLC2, a subunit of serine palmitoyltransferase, was overexpressed by adenovirus. Adenoviral overexpression of SPTLC2 (AdSPTLC2) decreased cell viability of HEK293 and HepG2 cells. In addition, AdSPTLC2 induced apoptosis via the caspase-dependent apoptotic pathway and elevated cellular ceramide, sphingoid bases, and dihydroceramide. However, overexpression of SPTLC2 did not induce ER stress. Collectively, celecoxib activates de novo sphingolipid biosynthesis and the combined effects of elevated ceramide and transcriptional activation of ER stress induce apoptosis. However, activation of de novo sphingolipid biosynthesis does not activate ER stress in hepatoma cells and is distinct from the celecoxib-mediated activation of ER stress.

• The Korean Journal of Zoology
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• v.14 no.2
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• pp.43-56
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• 1971

The Ca uptake by the fragmented sarcoplasmic reticulum of the rabbit skeletal muscle was measured under various concentrations of K, Mg, Caffeine, procaine and quinine. The ATPase activity of this reticular membrane was measured under the same conditions simultaneously. The saturation of Ca uptake was almost completed within 1 minute. The Ca uptake was inhibited by high concentrations of K (above 50 mM) and Mg (above 1 mM)in the absence of ATP. When ATP is present, however, the Ca uptake did not reflect the concentration of K, while it increased greatly as the concentration of Mg was increased. Caffeine and procaine caused the inhibition of Ca uptake in the presence of ATP, but quinine did not. The ATPase activity of the membrane was little affected by the concentration of K, while it was enhanced in the presence of Mg. Caffeine, procaine and quinine did not influence the ATPase activity.