• Title/Summary/Keyword: Orphan Cell

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Recent Progress in Orphan Nuclear Hormone Receptors

  • Lee, Yoon-Kwang;Tzameli, Iphigeoia;Zavacki, Ann Marie;Moore, David D.
    • BMB Reports
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    • v.31 no.5
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    • pp.419-426
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    • 1998
  • The nuclear hormone receptor superfamily currently includes approximately equal numbers of conventional receptors and orphan receptors, which do not have known ligands. Here, we review recent progress from this laboratory on three orphans, two of which are moving from orphan to conventional receptor status. Perhaps the most unusual is CAR, which is a constitutive transactivator in the absence of ligands but becomes transcriptionally inactive in the presence of its ligands, which are androgen metabolites. The response of CAR to its ligands is thus opposite to that of the conventional receptor paradigm. RIP14 (also known as FXR) is activated by both all-trans retinoic acid and a synthetic retinoid previously thought to specifically target the retinoic acid receptors (RARs), and thus appears to be a novel retinoid receptor. Finally, SHP is a novel orphan that lacks a DNA binding domain and interacts with a number of other receptor superfamily members. While it generally inhibits its targets, including CAR, the retinoid X receptor (RXR), and the estrogen receptor (ER), it stimulates transactivation by the orphan SF-1.

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A Study on the Nutritional Status of Children Living in Rural Area and City Orphan Asylum -II. Hematological view- (농어촌(農漁村)과 시설거주(施設居住) 아동(兒童)의 영양상태(營養狀態)에 관(關)한 연구(硏究) -제2보(第2報) : 혈액성장(血液性狀)을 중심(中心)으로-)

  • Park, Bock-Hee
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.14 no.2
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    • pp.108-116
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    • 1985
  • This study was designed to investigate the nutritional anemic state and hematological findings of children, aged 11 and 12 years, living in Haenam Koon (living at home) and in Mokpo City (living in an orphan asylum) located in Chonnam. The mean red blood cell number of male was higher than female in both groups of living in the rural area and in the city orphan asylum (p<0.01), but the white blood cell count was not significantly different. The levels of average hemoglobin, hematocrit and mean corpuscular hemoglobin concentration of the children in both groups were similar, and 19.8% of children living at home in the rural area and 32.1% of children living in the city orphan asylum were anemic. The mean levels of serum total protein, albumin and A/G ratio in children of both group were not statistically different, and 18.4% of children living at home in the rural area and 13.2% of children living in the city orphan asylum were insufficient in the serum total protein value. The average serum cholesterol level of children living at home in the rural area was higher than that of children living in the city orphan asylum(p<0.01), and that of female living at home was higher than that of male (p<0.05). The mean levels of serum iron, total iron binding capacity and transferrin saturation of children living at home in the rural area were significantly higher than those of children living in the city orphan asylum (p<0.01).

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APPLICATION OF MOVING LEAST SQUARE METHOD IN CHIMERA GRID METHOD (중첩격자에 대한 이동최소자승법 적용 연구)

  • Lee, K.;Lee, S.
    • 한국전산유체공학회:학술대회논문집
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    • 2007.04a
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    • pp.17-22
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    • 2007
  • Chimera grid Method is widely used in Computational Fluid Dynamics due to its simplicity in constructing grid system over complex bodies. Especially, Chimera grid method is suitable for unsteady flow computations with bodies in relative motions. However, interpolation procedure for ensuring continuity of solution over overlapped region fails when so-call orphan cells are present. We have adopted MLS(Moving Least Squares) method to replace commonly used linear interpolations in order to alleviate the difficulty associated with orphan cells. MSL is one of interpolation methods used in mesh-less methods. A number of examples with MLS are presented to show the validity and the accuracy of the method.

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EID-1 Interacts with Orphan Nuclear Receptor SF-1 and Represses Its Transactivation

  • Park, Yun-Yong;Park, Ki Cheol;Shong, Minho;Lee, Soon-Jung;Lee, Young-Ho;Choi, Hueng-Sik
    • Molecules and Cells
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    • v.24 no.3
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    • pp.372-377
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    • 2007
  • The orphan nuclear receptor, SF-1, plays a pivotal role in the development and differentiation of the endocrine and reproductive systems, and also regulates the transcription of a host of genes, including those encoding several steroidogenic enzymes and gonadotropins. We found that a previously unidentified repressor, EID-1, is an SF-1-interacting protein that inhibits the transactivation of SF-1. A transient transfection assay revealed that EID-1 inhibits SF-1, but not LRH-1, $ERR{\gamma}$, or mCAR. Using the yeast two hybrid and GST pull-down assays, we determined that EID-1 interacted strongly with SF-1. In addition, it colocalized with SF-1 in mammalian cells and interacted specifically with the AF-2 domain of SF-1, competing with SRC-1 to inhibit SF-1 transactivation. EID-1 is expressed in the mouse testis, and its expression decreases during testis development. The results of the present study suggest that EID-1 can act as a repressor, regulating the function of SF-1.

GPR78 promotes lung cancer cell migration and metastasis by activation of Gαq-Rho GTPase pathway

  • Dong, Dan-Dan;Zhou, Hui;Li, Gao
    • BMB Reports
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    • v.49 no.11
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    • pp.623-628
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    • 2016
  • GPR78 is an orphan G-protein coupled receptor (GPCR) that is predominantly expressed in human brain tissues. Currently, the function of GPR78 is unknown. This study revealed that GPR78 was expressed in lung cancer cells and functioned as a novel regulator of lung cancer cell migration and metastasis. We found that knockdown of GPR78 in lung cancer cells suppressed cell migration. Moreover, GPR78 modulated the formation of actin stress fibers in A549 cells, in a RhoA- and Rac1-dependent manner. At the molecular level, GPR78 regulated cell motility through the activation of $G{\alpha}q$-RhoA/Rac1 pathway. We further demonstrated that in vivo, the knockdown of GPR78 inhibited lung cancer cell metastasis. These findings suggest that GPR78 is a novel regulator for lung cancer metastasis and may serve as a potential drug target against metastatic human lung cancer.

Maternal killer-cell immunoglobulin-like receptors and paternal human leukocyte antigen ligands in recurrent pregnancy loss cases in Turkey

  • Elbasi, Mehmet Onur;Tulunay, Aysin;Karagozoglu, Hale;Kahraman, Semra;Eksioglu-Demiralp, Emel
    • Clinical and Experimental Reproductive Medicine
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    • v.47 no.2
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    • pp.122-129
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    • 2020
  • Objective: The survival of a semi-allogeneic fetus depends on several immunological mechanisms, and it has been suggested that recurrent pregnancy loss (RPL) could develop as a result of one or more immunological abnormalities. Methods: Compatibility between partners for human leukocyte antigen (HLA) genotypes and the relationships between maternal killer-cell immunoglobulin-like receptor (KIR) and paternal HLA-Bw4/Bw6 and HLA-C1/C2 supra-groups were investigated in 25 couples with RPL in comparison to healthy couples with children. HLA and KIR genotyping was performed using polymerase chain reaction with sequence-specific primers and/or sequence-specific oligonucleotides. Results: HLA class I incompatibility between partners, especially in HLA-B alleles, was more common in the RPL group (p= 0.01). HLA-C2 homozygosity was more frequent in the male partners of RPL couples than in other groups (p= 0.03). The KIR2DL5 gene frequency was significantly higher in both the female and male partners of RPL couples, whereas the KIR2DS3 gene frequency in male partners of RPL couples was significantly reduced (p= 0.03). The presence of KIR2DL3 in women with RPL was correlated with the presence of HLA-C2 alleles in their spouses (p= 0.03). Conclusion: Our data from a Turkish population suggest that male HLA-C2 homozygosity may play an important role in RPL. Additionally, an incidental match between male HLA-C2 and female HLA-C1 ligand KIR receptors might perturb the balance between activatory and inhibitory KIR-ligand interactions during pregnancy in couples affected by RPL. The roles of orphan KIR2DL5 and orphan KIR2DS3 in RPL remain obscure.

The Nuclear Orphan Receptor NR4A1 is Involved in the Apoptotic Pathway Induced by LPS and Simvastatin in RAW 264.7 Macrophages

  • Kim, Yong Chan;Song, Seok Bean;Lee, Sang Kyu;Park, Sang Min;Kim, Young Sang
    • IMMUNE NETWORK
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    • v.14 no.2
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    • pp.116-122
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    • 2014
  • Macrophage death plays a role in several physiological and inflammatory pathologies such as sepsis and arthritis. In our previous work, we showed that simvastatin triggers cell death in LPS-activated RAW 264.7 mouse macrophage cells through both caspase-dependent and independent apoptotic pathways. Here, we show that the nuclear orphan receptor NR4A1 is involved in a caspase-independent apoptotic process induced by LPS and simvastatin. Simvastatin-induced NR4A1 expression in RAW 264.7 macrophages and ectopic expression of a dominant-negative mutant form of NR4A1 effectively suppressed both DNA fragmentation and the disruption of mitochondrial membrane potential (MMP) during LPS- and simvastatin-induced apoptosis. Furthermore, apoptosis was accompanied by Bcl-2-associated X protein (Bax) translocation to the mitochondria. Our findings suggest that NR4A1 expression and mitochondrial translocation of Bax are related to simvastatin-induced apoptosis in LPS-activated RAW 264.7 macrophages.

Tributyltin Induces Orphan Nuclear Receptor Nur77 Gene Expression and Cell Death in Testicular cell line (TM3)

  • Lee, Kyung-Hee;Lee, Kyung-Jin;Bin, Im-Wook;Park, Hueng-Sik;Lee, Jong-Bin
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2002.11b
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    • pp.168-168
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    • 2002
  • A clear association between occupational tributyltin (TBT) exposure and testicular cell line, TM3 has been observed in mouse. In the present study, we have investigated cytotoxic effects of TBT on Significant cytolethality was observed in TM3 cells in a time- and concentration-dependent manner when measured by MTT assays. (omitted)

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Orphan Nuclear Receptor Nurr1 as a Potential Novel Marker for Progression in Human Prostate Cancer

  • Wang, Jian;Yang, Jing;Zou, Ying;Huang, Guo-Liang;He, Zhi-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.3
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    • pp.2023-2028
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    • 2013
  • A number of studies have indicated that Nurr1, which belongs to a novel class of orphan nuclear receptors (the NR4A family), is important for carcinogenesis. Here we investigated expression of Nurr1 protein in benign and malignant human prostate tissues and association with clinicopathologic features using immunohistochemical techniques. Moreover, we also investigated the ability of Nurr1 to influence proliferation, migration, invasion and apoptosis of human prostate cancer cells using small interfering RNA silencing. Immunohistochemical analysis revealed that the expression of Nurr1 protein was higher in prostate cancer tissues than in benign prostate tissue (P<0.001), levels being positively correlated with tumor T classification (P = 0.003), N classification (P = 0.017), M classification (P = 0.011) and the Gleason score (P = 0.020) of prostate cancer patients. In vitro, silencing of endogenous Nurr1 attenuated cell proliferation, migration and invasion, and induced apoptosis of prostate cancer cells. These results suggest that Nurr1 may be used as an indicator for prostate cancer progression and be useful for novel potential therapeutic strategies.