• Title/Summary/Keyword: Cytoplasmic Effects

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The Cross-talk Mechanisms of Constitutive Androstane Receptor (CAR) in the Regulation of its Activity, Energy Metabolism, Cellular Proliferation and Apoptosis (Constitutive Androstane Receptor (CAR)의 활성, 에너지 대사 및 세포의 증식과 사멸의 조절에 대한 CAR의 cross-talk 기전)

  • Min, Gyesik
    • Journal of Life Science
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    • v.30 no.2
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    • pp.211-220
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    • 2020
  • The activity of CAR can be regulated not only by ligand binding but also by phosphorylation of regulatory factors involved in extracellular signaling pathways, cross-talk interactions with transcription factors, and the recruitment, degradation, and expression of coactivators and corepressors. This regulation of CAR activity can in turn have effects on the control of diverse physiological homeostasis, including xenobiotic and energy metabolism, cellular proliferation, and apoptosis. CAR is phosphorylated by the ERK1/2 signaling pathway, which causes formation of a complex with Hsp-90 and CCRP, leading to its cytoplasmic retention, whereas phenobarbital inhibits ERK1/2, which causes dephosphorylation of the downstream signaling molecules, leading to the recruitment to CAR of the activated RACK-1/PP2A components for the dephosphorylation, nuclear translocation, and the transcriptional activation of CAR. Activated CAR cross-talks with FoxO1 to induce inhibition of its transcriptional activity and with PGC-1α to induce protein degradation by ubiquitination, resulting in the transcriptional suppression of PEPCK and G6Pase involved in gluconeogenesis. Regulation by CAR of lipid synthesis and oxidation is achieved by its functional cross-talks, respectively, with PPARγ through the degradation of PGC-1α to inhibit expression of the lipogenic genes and with PPARα through either the suppression of CPT-1 expression or the interaction with PGC-1α each to induce tissue-specific inhibition or stimulation of β-oxidation. Whereas CAR stimulates cellular proliferation by suppressing p21 expression through the inhibition of FoxO1 transcriptional activity and inducing cyclin D1 expression, it suppresses apoptosis by inhibiting the activities of MKK7 and JNK-1 through the expression of GADD45B. In conclusion, CAR is involved in the maintenance of homeostasis by regulating not only xenobiotic metabolism but also energy metabolism, cellular proliferation, and apoptosis through diverse cross-talk interactions with extracellular signaling pathways and intracellular regulatory factors.

The Test of Combining Ability and Heterosis on the Silkworm(Bombyx mori) Breeding (누에 견.사질에 관한 잡종강세 및 조합능력검정)

  • 문병원;한경수
    • Journal of Sericultural and Entomological Science
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    • v.36 no.1
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    • pp.8-25
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    • 1994
  • The study was conducted to obtain the genetic information on heterosis and combining ability of the quantitative characters for F1 hybrid breeding in silkworms. Six parental varieties and each set of 30 diallel crosses in F1's were used as materials, and bred on the randomized complete block design with three replications. Fourteen characters were observed with the twenty samples in each tray. The data were analyzed for (1) heterosis and combining ability in F1 hybrid. The heterosis in the weight and the length of cocoon showed positively high at 24.51%, and 23.4%, respectively and the weight of the whole cocoon as well as the weight of the whole cocoon layer showed a siginificant heterosis ranging from 15.56% to 15.71% and from 17.14% to 19.01%, but the fifth and the total instar period showed negative heterosis. It was found that the combination between, C70XRomogua and N9 X Romogua showed highly a negative heterosis on the fifth instar period and for the cocoon weight. The female of N9+Sansuian and the male of Romogua X Sansurian have a high heterosis effect, on the cocoon shell weight, and Sansurian X Romogua(reciprocal) on the length and the weight of cocoon filament with no regard to sexuality. The significant maternal and cytoplasmic effect on heterosis of the cocoon weight and the cocoon shell weight were observed with the combinations, N9 X C5, N63 X C70 and on the length of the cocoon filament with the combinations, Sansurian X N63, Sansurian X C5, Sansurian X C70 and N9 X C70, N63 X C70 on the weight of cocoon filament. As mean squared of GCA, SCA and RCA were significant with these combining ability for all characters resulted from additive and non-additive altogether and there is a significant difference between reciprocals. Sansurian showed a negative GCA effect on the fifth and total larval duration, but the higher positive GCA effects took places with varieties N9 and C5 on the length, width, weight of cocoon, cocoon shell weight, percentage of cocoon shell weight, length and weight of cocoon filament, percentage of raw-silk with no regard to both generations and silkworm sexuality. The values of SCA between the cross combinations varied generation-wise and sex-wise. It was shown that SCA value for the fifth instar period was highly negative for Sansurian X C70, Romogua X C70, Sansurian X C5, Romogua X C5, but it was positive effect on the cocoon weight, cocoon shell weight with N9 X C5, and C70 X Sansurian, on the length of cocoon filament with N9 X C5, Romogua X Sansurian on the weight of cocoon filament between Romogua and N63 and on the percentage of raw-silk between the combination of Sansurian X Romoga.

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Reduction of Mitochondrial Electron Transferase in Rat Bile duct Fibroblast by Clonorchis sinensis Infection (간흡충(Clonorchis sinensis)감염에 의한 흰쥐 담관 섬유모세포 미토콘드리아 전자전달효소의 감소)

  • Min, Byoung-Hoon;Hong, Soon-Hak;Lee, Haeng-Sook;Kim, Soo-Jin;Joo, Kyoung-Hwan
    • Applied Microscopy
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    • v.40 no.2
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    • pp.89-99
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    • 2010
  • Fibroblasts are the most common cells in connective tissue and are responsible for the synthesis of extracellular matrix components. The fibrosis associated with chronic inflammation and injury may contribute to cholangiocarcinoma pathogenesis, particularly through an increase in extracellular matrix components, which participate in the regulation of bile duct differentiation during development. Mitochondria produce ATP through oxidative metabolism to provide energy to the cell under physiological conditions. Also, mitochondrial dysfunction and oxidative stress have been implicated in cellular senescence and aging. Alternations in mitochondrial structure and function are early events of programmed cell death or apoptosis and mitochondria appear to be a central regulator of apoptosis in most somatic cell. Clonorchis sinensis, one of the most important parasite of the human bile duct in East Asia, arouses epithelial hyperplasia and ductal fibrosis. Isolated fibroblast from the bile ducts of rats infected by C. sinensis showed increase of cytoplasmic process. In addition, decrease of cellular proliferation was observed in fibroblasts which was isolated from normal rat bile duct and then cultured in media containing C. sinensis excretory-secretory product. However, the effects of C. sinensis infection on the mitochondrial enzyme distribution is not clearly reported yet. Therefore, we investigated the structural change of C. sinensis infected bile duct and mitochondrial enzyme distribution of the cultured fibroblast isolated from the C. sinensis infected rat bile duct. As a result, C. sinensis infected SD rat bile ducts showed the features of chronic clonorchiasis, such as ductal connective and epithelial tissue dilatation, or ductal fibrosis. In addition, fibroblast in ductal connective tissue was damaged by physical effect of fibrotic tissue and chemical stimulation. Immunohistochemically detected mitochondrial electron transferase (ATPase, COXII, Porin) was decreased in C. sinensis infected rat bile duct and cultured fibroblast from infected rat bile duct. It can be hypothesized that the reason why number of electron transferase decrease in fibroblast isolated from the rat bile duct infected with C. sinensis is because dysfunction of electron transport system is occurred mitochondrial dysfunction, increase of ROS (reactive oxygen species) and apoptosis after chemical damage on the cell caused by C. sinensis infection. Overall, C. sinensis infection induces fibrotic change of ductal connective tissue, mutation of cellular metabolism in fibroblast and mitochondrial dysfunction. Consequently, ductal fibrosis inhibits fibroblast proliferation and decreases mitochondrial electron transferase on fibroblast cytoplasm. It was assumed that the structure of bile duct could not normalized and ductal fibrosis was maintained for a long period of time according to fibroblast metamorphosis and death induced by mitochondrial dysfunction.

Effects of Flushing, Preservation and Reperfusion in the Canine Transplanted Lung Tissue (관류, 보존 및 재관류 과정이 이식된 개의 폐조직에 미치는 영향)

  • Lim, Young-Keun;Park, Chang-Kwon;Kwon, Kun-Young
    • Tuberculosis and Respiratory Diseases
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    • v.46 no.4
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    • pp.512-522
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    • 1999
  • Background: Due to the paucity of suitable donor organs for lung allotransplantation, a number of techniques have been developed to improve the lung preservation. Ultrastructural studies of the morphologic changes of the flushing, preservation and reperfusion injury in donor lungs have rarely been reported. Methods: Adult dogs (n=46) were matched as donors and recipients for the single lung transplantation. The donor lungs were preserved after flushing with preservation solution and transplanted after 20-hours of preservation at $10^{\circ}C$. Ultrastructural features of the lung were examined after flushing, preservation and 2 hours after lung transplantation (reperfusion) respectively. Results: Electron microscopy after flushing showed focal alveolar collapse and mild swelling of type I epithelial cells. After preservation both type I epithelial cells and endothelial cells were swollen and destroyed focally. The endothelial cells showed protrusion of tactile-like structures into the lumina, blebs or vacuoles of the cytoplasm After reperfusion the lung tissue showed fibrin material in the alveoli, prominent type I epithelial cell swelling with fragmented cytoplasmic debris and marked endothelial cell swelling with vacuoles or tactile-like projections. The alveolar macrophages showed active phagocytosis. Scanning electron microscopic examination of the pulmonary parenchyma showed focally alveolar collapse and focal consolidation after the preservation and more prominent changes after the reperfusion procedure. The lungs preserved with low potassium dextran glucose solution, with additional prostaglandin $E_1(PGE_1)$ and verapamil(VP) showed relatively well preserved ultrastructures compared with those which were preserved with modified Euro-Collins or University of Wisconsin, and with additional $PGE_1$ and/or VP. Conclusion: The ultrastructural changes associated with flushing were mild in severity, the donor lungs were injured during the preservation, and further damage was occurred during the reperfusion. The reperfusion injury resulted in prominent pulmonary parenchymal alterations with a pattern of acute lung injury.

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THE EFFECTS OF VARIOUS TETRACYCLINE HCL CONCENTRATION TREATED ROOW SURFACES ON PROLIFERATION AND SPREADING OF PERIODONTAL LIGAMENT CELLS (다양한 농도의 테트라사이클린로 처리된 치근면이 치주인대세포의 증식과 전개에 미치는 영향)

  • Jung, Oh-Chul;Sun, Jo-Young
    • Journal of Periodontal and Implant Science
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    • v.24 no.3
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    • pp.581-596
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    • 1994
  • This in vitro study was undertaken to obtain optimal tetracycline concentration that aids proliferation and spreading of human periodontal ligament cells, for clinical application in root surfaces of periodontally diseased teeth. Periodontal ligament cells used in this study were obtained from explants of periodontal ligament of 1st premolar teeth which were extracted for the purpose of orthodontic treatment. The cells were cultured in Dulbecco's Modified Eagle Medium(DMEM) supplemented with 100 U/ml penicillin, $100\;{\mu}g/ml$ streptomycin and 10% FBS at $37^{\circ}C$, 100% humidity, 5% $CO_2-95%$ air. Cells were used between the third to 4th passage. After root planing of periodontally extracted teeth, the root slabs were cut with carborundum disk. In the cell proliferation experiment, experimental groups were root planing only group, immersed groups in 25, 50, 75, 100, 150mg/ml aqueous solution of Tetracycline HCl followed by a vigorous rinse in PBS. Human PDL cells at concentration of $1{\times}10^5\;cells/ml$ were seeded in each culture well which contained root slabs and incubated for 6 hours. Then, all of the root slabs were moved into new 24 culture well and incubated 24, 48 and 72 hours. The cell counting was done by inverted phase contrast microscope after trypsinization. The following results were obtained. The cell number was increased in order root planing only group, 25, 150, 50, 75, 100mg/ml of Tetracycline HCl treated group in 24, 48 and 72 hours. The maximal cell number was obtained when the root slabs were immersed in solution with 100mg/ml of Tetracycline HCl. There were statistically significant between the root planing only group and 75, 100 mg/ml of Tetracycline HCl treated group in 24 hours, between the root planing only group and 100mg/ml of Tetracycline HCl treated group in 48 hours, between the root planing only group and 50, 75, 100mg/ml of Tetracycline HCl treated group, between 25 and 100mg/ml of Tetracycline HCl treated group in 72 hours(p<0.05). In the cell spreading experiment, after 30 minutes of incubated, in the root planing only group, the cells were generally round in shape. The cell surface was mostly covered with blebs. The cells started to attach to root surface by cytoplasmic extension in 50, 100mg/ml of Tetracycline HCl treated groups, more numerous cells attached to root surface than root planing only group. Many orifices of dentinal tubule were exposed, cells showed radially spreaded cytoplasm and unspreaded central region of the cell was covered with blebs. After 6 hours of incubation, in the root planing only group, cells showed radially spreaded cytoplasm and were attached flat appearance. In 50, 100mg/ml of Tetracycline HCl treated groups, cellular margin was concaved and cytoplasm showed elongated appearance with polarity. After 24 hours of incubation, in the root planing group, cells showed characteristic polarity. In 50, 100mg/ml of Tetracycline HCl treated groups, cells showed more elongated and spindle - like appearance.

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