• Title/Summary/Keyword: ER-${\alpha}$

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FMDV 2C Protein of Foot-and-mouth Disease Virus Increases Expression of Pro-inflammatory Cytokine TNFα via Endoplasmic Reticulum Stress (구제역바이러스의 FMDV 2C 단백질은 소포체 스트레스를 통해서 염증 유도 사이토카인 TNFα의 발현을 증가시킴)

  • Kang, Hyo Rin;Seong, Mi So;Nah, Jin Ju;Ryoo, Soyoon;Ku, Bok Kyung;Cheong, JaeHun
    • Journal of Life Science
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    • v.30 no.3
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    • pp.285-290
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    • 2020
  • Foot-and-mouth disease virus (FMDV), a member of the genus Aphthovirus in the Picornaviridae family, affects wild and domesticated ruminants and pigs. FMDV causes various clinical symptoms, including severe inflammation in infected tissue. Genome RNA of FMDV shows a positive single-strand chain approximately 8.3 kb long and encodes a single long open reading frame (ORF). The ORF is translated into structural and non-structural proteins by viral proteases. The FMDV 2C protein is one of the non-structural proteins encoded by FMDV and plays a critical role in FMD pathogenesis, including inflammation, apoptosis, and viral replication. In this study, we examined whether FMDV 2C induces intracellular expression of pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). FMDV 2C expression in pig IBRS-2 cells increased mRNA and protein expression of TNFα at the transcriptional level via activation of TNFα promoter. Treatment with 4-phenylbutyric acid, an endoplasmic reticulum (ER) stress reducer, decreased TNFα expression induced by FMDV 2C. Activating transcription factor 4 (ATF4), a transcription factor mediating ER stress response, induced transactivation of TNFα promoter and expression of mRNA and protein of TNFα. However, the dominant negative mutant of ATF4 did not induce FMDV 2C-mediated TNFα expression. The results indicate that FMDV 2C protein increases clinical inflammation via ATF4-mediated TNFα expression and is associated with ER stress induction.

Osteogenic Response of Human Osteoblasts Derived from Mandible and Maxilla: A Preliminary Study (상, 하악골 유래 조골세포의 골형성 능: 일차 연구)

  • Yang, Hoon Joo;Song, Yoon Mi;Kim, Ri Youn;Oh, Ji Hye;Cho, Tae Hyung;Kim, In Sook;Hwang, Soon Jung
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.35 no.1
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    • pp.31-37
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    • 2013
  • Purpose: Maxilla and mandible have different patterns of cortical and trabecular bone and different bone mineral densities, even though both are components of the jaw bone. However, cellular differences between maxilla- and mandible derived osteoblasts (OBs) have rarely been studied. We hypothesize that maxilla- and mandible-derived OBs show different responses to $17{\beta}$-estradiol (E2), which is one of the critical factors for bone formation. This study compares skeletal site-specific cell responses between maxilla- and mandible-derived human OBs to E2. Methods: Maxilla- and mandible-derived OBs derived from an identical donor were separately isolated from a total of five normal healthy subjects aged 18~44 years old, cultured with a treatment of 100 nM estrogen. The responses between maxilla- and mandible-derived OBs to E2 were evaluated and compared using cell proliferation, alkaline phosphatase (ALP) activity and gene expression of osteoprotegerin (OPG), ALP, insulin-like growth factor-1 (IGF-1), and estrogen receptor ${\alpha}$ ($ER{\alpha}$). Results: E2 did not have any distinct effects on the proliferation of both types of OBs. Mandible-derived OBs exhibited higher ALP activity than maxilla-derived OBs in the non-treated condition, which was common in all tested individuals. ALP activities of both types of OBs showed a minor increasing tendency with the treatment of E2, even though there was no statistical significance in some specimens. The gene expression of OB by E2 was diverse, depending on the individuals. There was increased expression of OPG, IGF-1, or $ER{\alpha}$ gene in the part of subjects, which was more repeated in maxilla-derived OBs. In particular, OPG or ALP induction by E appeared less frequently in mandible-derived OBs. Conclusion: Current results revealed that E2 affects maxilla- and mandible-derived OBs into facilitating the osteogenic process despite individual differences. Mandible-derived OBs are less sensitive to bone-forming gene expression by E2.

Modulation of G-CSF Secretion by Mutations of Non Alpha-Helical Region in N-Terminus (G-CSF 단백질 N-말단의 비 알파-Helix 영역의 돌연변이에 의한 분비 조절)

  • Park, Jeong-Hae;Park, Jung-Ae;Kang, Seok-Woo;Goo, Tae-Won;Chung, Kyung-Tae
    • Journal of Life Science
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    • v.21 no.12
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    • pp.1778-1783
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    • 2011
  • Hematopoietic cytokines regulate production of blood cells by stimulating proliferation and differentiation of bone marrow cells. Among these hematopoietic cytokines, called hematopoitic growth factors, glranulocyte-colony stimulating Factor (G-CSF), which regulates growth of neutrophils, is one of important therapeutic factors because cancer patients suffer with neutropenia which is severe reduction of neutrophils after chemotherapy. Two groups of recombinant G-CSF have approved and used for therapeutic purposes and many researches are still on-going to produce recombinant G-CSF by different techniques. We engineered human G-CSF with Bombyx specific endoplasmic reticulum (ER) signal sequence, therefore, secretion of human G-CSF protein was improved in Bombyx mori-origined cell line, Bm5. The Bombyx ER signal sequence and human G-CSF matured protein region chimera was further remodeled at the N-terminus of matured G-CSF protein to understand roles of N-terminus on outer cellular secretion and/or production. Three different mutants were generated deleting three amino acids in non alpha-helical region in N-terminus in order to scan important amino acids for G-CSF secretion. One of 3 different N-terminal deletion mutants showed dramatically reduction of secreted amount of G-CSF indicating its important role on secretion. The data suggest that remodeling in non alpha-helical region of N-terminus is also important for recombinant G-CSF production.

Antistress effect of red ginseng in brain cells is mediated by TACE repression via PADI4

  • Kim, Eun-Hye;Kim, In-Hye;Ha, Jung-Ah;Choi, Kwang-Tae;Pyo, Suhkneung;Rhee, Dong-Kwon
    • Journal of Ginseng Research
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    • v.37 no.3
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    • pp.315-323
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    • 2013
  • Ginseng is known to have antistress effects. Previously, red ginseng (RG) was shown to repress stress-induced peptidyl arginine deiminase type IV (PADI4) via estrogen receptor ${\beta}$ ($ER{\beta}$) in the brain, thus inhibiting brain cell apoptosis. Moreover, tumor necrosis factor (TNF)-${\alpha}$ plays a critical role in immobilization (IMO) stress. However, the signaling pathway of RG-mediated repressesion of inflammation is not completely understood. In this study, we determined how RG modulated gene expression in stressed brain cells. Since secretion of TNF-${\alpha}$ is modulated via TNF-${\alpha}$ converting enzyme (TACE) and nuclear factor (NF)-${\kappa}B$, we examined the inflammatory pathway in stressed brain cells. Immunohistochemistry revealed that TACE was induced by IMO stress, but RG repressed TACE induction. Moreover, PADI4 siRNA repressed TACE expression compared to the mock transfected control suggesting that PADI4 was required for TACE expression. A reporter assay also revealed that $H_2O_2$ oxidative stress induced NF-${\kappa}B$ in neuroblastoma SK-N-SH cells, however, RG pretreatment repressed NF-${\kappa}B$ induction. These findings were supported by significant induction of nitric oxide and reactive oxygen species (ROS) by oxidative stress, which could be repressed by RG administration. Taken together, RG appeared to repress stress-induced PADI4 via TACE and NF-${\kappa}B$ in brain cells thus preventing production of ROS and subsequently protecting brain cells from apoptosis.

Salubrinal Alleviates Pressure Overload-Induced Cardiac Hypertrophy by Inhibiting Endoplasmic Reticulum Stress Pathway

  • Rani, Shilpa;Sreenivasaiah, Pradeep Kumar;Cho, Chunghee;Kim, Do Han
    • Molecules and Cells
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    • v.40 no.1
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    • pp.66-72
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    • 2017
  • Pathological hypertrophy of the heart is closely associated with endoplasmic reticulum stress (ERS), leading to maladaptations such as myocardial fibrosis, induction of apoptosis, and cardiac dysfunctions. Salubrinal is a known selective inhibitor of protein phosphatase 1 (PP1) complex involving dephosphorylation of phospho-eukaryotic translation initiation factor 2 subunit $(p-eIF2)-{\alpha}$, the key signaling process in the ERS pathway. In this study, the effects of salubrinal were examined on cardiac hypertrophy using the mouse model of transverse aortic constriction (TAC) and cell model of neonatal rat ventricular myocytes (NRVMs). Treatment of TAC-induced mice with salubrinal ($0.5mg{\cdot}kg^{-1}{\cdot}day^{-1}$) alleviated cardiac hypertrophy and tissue fibrosis. Salubrinal also alleviated hypertrophic growth in endothelin 1 (ET1)-treated NRVMs. Therefore, the present results suggest that salubrinal may be a potentially efficacious drug for treating pathological cardiac remodeling.

Isolation and Characterization of a Novel Transcription Factor ATFC Activated by ER Stress from Bombyx mori Bm5 Cell Lines (누에 배양세포(Bm5)로부터 분리한 새로운 전사제어인자 ATFC의 특성분석)

  • 구태원;윤은영;김성완;최광호;황재삼;박수정;권오유;강석우
    • Journal of Life Science
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    • v.13 no.5
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    • pp.596-603
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    • 2003
  • Cells respond to an accumulation of unfolded proteins in the endoplasmic reticulum (ER) by increasing transcription of genes encoding molecular chaperones and folding enzymes. The information is transmitted from the ER lumen to the nucleus by intracellular signaling pathway, called the unfolded protein response (UPR). To obtain genes related to UPR from B. mori, the cDNA library was constructed with mRNA isolated from Bm5 cell lines in which N-glycosylation was inhibited by tunicamycin treatment. From the cDNA library, we selected 40 clones that differentially expressed when cells were treated with tunicamycin. Among these clones, we have isolated ATFC gene showing similarity with Hac1p, encoding a bZIP transcription factor of 5. cerevisiae. Basic-leucine zipper (bZIP) domain in amino acid sequences of ATFC shared homology with yeast Hac1p. Also, ATFC is up-regulated by accumulation of unfolded proteins in the ER through the treatment of ER stress drugs. Therefore we suggest that ATFC represents a major component of the putative transcription factor responsible for the UPR leading to the induction of ER-localized stress proteins.

Development of Meander-shaped Metallic Magnetic Calorimeters

  • Yoon, W.S.;Jang, Y.S.;Kim, G.B.;Lee, H.J.;Lee, J.Y.;Lee, M.K.;Kim, Y.H.
    • Progress in Superconductivity
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    • v.14 no.2
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    • pp.102-105
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    • 2012
  • We are developing meander-shaped metallic magnetic calorimeters using micro-fabrication methods. A planar Nb coil in a meander shape was fabricated on a Si substrate. The coil was designed to have a persistent current using a metal heater evaporated on a part of the coil. A paramagnetic sensor, $5{\mu}m$ thick Au:Er foil, was glued on top of the meander structure with epoxy. The magnetization and heat capacity were measured at different temperatures, and applied field currents matched well with expected values. The detector showed an energy resolution of 4 keV FWHM for the 5.5 MeV alpha particles.

The Differential Gene Expression Patterns in Endometrial Tissue of Sows in Early Gestation

  • Kim, Bong-Ki;Chung, Hak-Jae;Ko, Yeoung-Gyu;Lee, Hwa-Young;Woo, Jei-Hyun;Kim, Young-Mi;Bae, Young-Eun;Kim, Jeom-Soon;Jung, Jin-Kwan;Chang, Won-Kyong
    • Proceedings of the KSAR Conference
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    • 2004.06a
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    • pp.235-235
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    • 2004
  • Although studies for important genes concerned in preimplantation stage that encompasses the period from fertilization to implantation were reported for mice and cows, little information relevant to this subject is known in pigs. (omitted)

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An analysis of complex permeability of Mn-Zn ferrite doped with rare earth oxide. (희토류가 첨가된 Mn-Zn ferrite의 복소투자율 분석)

  • 김성수;최우성
    • Proceedings of the Korean Institute of Navigation and Port Research Conference
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    • 2000.11a
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    • pp.93-96
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    • 2000
  • In this study, we investigated the electromagnetic properties of Mn-Zn ferrite doped with rare earth oxide (Dy$_2$O$_3$, Er$_2$O$_3$). The main composition is 52mo1% $\alpha$-Fe$_2$O$_3$, 25mo1% Mn$_3$O$_4$23mo1% ZnO and doped with them(0.05wt%~0.25wt%, step:0.05wt%). An experimental process has advanced by conventional ferrimagnetism manufacturing that was prepared by standard ceramic techniques. The XRD pattern of all doped sample were observed spinel and secondary phase. The density of sample were measured nearly constant value. As increased the additive, resistivity, initial permeability and real component of the series complex permeability increased with setting limits each other. In case of Mn-Zn ferrite excess doped with them, resistivity, initial permeability and real component of the series complex permeability decreased and magnetic loss increased in proportion to increasing the additive.

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An analysis of complex permeability of Mn-Zn ferrite doped with rare earth oxide (희토류가 첨가된 Mn-Zn ferrite의 복소투자율 분석)

  • 김성수;최우성
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2000.11a
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    • pp.93-96
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    • 2000
  • In this study, we investigated the electromagnetic properties of Mn-Zn ferrite doped with rare earth oxide (Dy$_2$O$_3$, Er$_2$O$_3$). The main composition is 52mo1% ${\alpha}$-Fe$_2$O$_3$, 25mol% Mn$_3$O$_4$ 23mo1% ZnO and doped with them(0.05wt% ∼ 0.25wt%, step:0.05wt%). An experimental process has advanced by conventional ferrimagnetism manufacturing that was prepared by standard ceramic techniques. The XRD pattern of all doped sample were observed spinel and secondary phase. The density of sample were measured nearly constant value. As increased the additive, resistivity, initial permeability and real component of the series complex permeability increased with setting limits each other. In case of Mn-Zn ferrite excess doped with them, resistivity, initial permeability and real component of the series complex permeability decreased and magnetic loss increased in proportion to increasing the additive.

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