• 제목/요약/키워드: Orphan

검색결과 117건 처리시간 0.029초

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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    • 제14권3호
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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.

High Cytoplasmic Expression of the Orphan Nuclear Receptor NR4A2 Predicts Poor Survival in Nasopharyngeal Carcinoma

  • Wang, Jian;Yang, Jing;Li, Bin-Bin;He, Zhi-Wei
    • Asian Pacific Journal of Cancer Prevention
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    • 제14권5호
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    • pp.2805-2809
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    • 2013
  • Objective: This study aimed at investigating whether the orphan nuclear receptor NR4A2 is significantly associated with clinicopathologic features and overall survival of patients with nasopharyngeal carcinoma (NPC). Methods: Immunohistochemistry was performed to determine NR4A2 protein expression in 84 NPC tissues and 20 non-cancerous nasopharyngeal (NP) tissues. The prognostic significance of NR4A2 protein expression was evaluated using Cox proportional hazards regression models and Kaplan-Meier survival analysis. Results: We did not find a significant association between total NR4A2 expression and clinicopathological variables in 84 patients with NPC. However, we observed that high cytoplasmic expression of NR4A2 was significantly associated with tumor size (T classification) (P = 0.006), lymph node metastasis (N classification) (P = 0.002) and clinical stage (P = 0.017). Patients with higher cytoplasmic NR4A2 expression had a significantly lower survival rate than those with lower cytoplasmic NR4A2 expression (P = 0.004). Multivariate Cox regression analysis analysis suggested that the level of cytoplasmic NR4A2 expression was an independent prognostic indicator for overall survival of patients with NPC (P = 0.033). Conclusions: High cytoplasmic expression of NR4A2 is a potential unfavorable prognostic factor for patients with NPC.

Regioselective Oxidation of Lauric Acid by CYP119, an Orphan Cytochrome P450 from Sulfolobus acidocaldarius

  • Lim, Young-Ran;Eun, Chang-Yong;Park, Hyoung-Goo;Han, Song-Hee;Han, Jung-Soo;Cho, Kyoung-Sang;Chun, Young-Jin;Kim, Dong-Hak
    • Journal of Microbiology and Biotechnology
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    • 제20권3호
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    • pp.574-578
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    • 2010
  • Archaebacteria Sulfolobus acidocaldarius contains the highly thermophilic cytochrome P450 enzyme (CYP119). CYP119 possesses stable enzymatic activity at up to $85^{\circ}C$. However, this enzyme is still considered as an orphan P450 without known physiological function with endogenous or xenobiotic substrates. We characterized the regioselectivity of lauric acid by CYP119 using the auxiliary redox partner proteins putidaredoxin (Pd) and putidaredoxin reductase (PdR). Purified CYP119 protein showed a tight binding affinity to lauric acid ($K_d=1.1{\pm}0.1{\mu}M$) and dominantly hydroxylated (${\omega}-1$) position of lauric acid. We determined the steady-state kinetic parameters; $k_{cat}$ was 10.8 $min^{-1}$ and $K_m$, was 12 ${\mu}M$. The increased ratio to $\omega$-hydroxylated production of lauric acid catalyzed by CYP119 was observed with increase in the reaction temperature. These studies suggested that the regioselectivity of CYP119 provide the critical clue for the physiological enzyme function in this thermophilic archaebacteria. In addition, regioselectivity control of CYP119 without altering its thermostability can lead to the development of novel CYP119-based catalysts through protein engineering.

Remediation of Contaminated Sites in Canada

  • Koo, Jahak
    • 한국지하수토양환경학회:학술대회논문집
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    • 한국지하수토양환경학회 1996년도 경북지부 결성 및 추계학술발표회 논문집
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    • pp.39-49
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    • 1996
  • Hundreds of contaminated sites have been generated due to the past mismagement of toxic substances, the lack of adequate environmental controls and ignorance of the potential environmental impacts of general activities in Canada. The general public, industry and governments have been addressing the contaminated sites with a number of cleanup responses. Environmental protection and remediation have become top priorities for the public and private sectors alike in Canada. Between the late 1980s and the early 1990s, the Canadian Environmental Protection Act and Canada's Green Plan were followed by provincial and territorial laws and policies to regulate contaminated sites. The National Contaminated Site Remediation Program(NCSRP) was initiated in 1989. It has been administered through bilateral agreements between the federal and participating provincial/territorial governments. They have committed a total of $250 million toward orphan site cleanup and technology development/demonstration over a five year period. The federal government has committed an additional $25 million to assess contaminated sites on federal crown land. Over 40 orphan high-risk contaminated sites, over 230 federal sites and over 35 technology development/demonstration projects have been addressed. The Canadian Council of Ministers of the Environment has developed a series of guidance documents to ensure a consistent and successful implementation of the Program. The management/regulation scheme of contaminated sites generally consists of: 1) identifying and investigating sites, 2) determining site contamination, 3) recognizing responsibility and liability, 4) assessing priority for remediation, 5) activation, evaluation and implementing remediation options, and 6) documenting remediation completion. The NCSRP supported the successful development/demonstration of a wide range of innovative remedial technologies. They are related to stabilization/solidification, thermal washing/flushing, advanced oxidation, sonics, and groundwater contaminated with hydrocarbons, PAHS, PCBs, heavy metals, and other hazardous pollutants in a variety of site environments.

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한우 자궁내막염에서 발현 변화를 보이는 유전자 (Gene Expression Altered in Endometrium of Korean Cattle with Endometritis)

  • 강다원
    • Reproductive and Developmental Biology
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    • 제31권3호
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    • pp.207-213
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    • 2007
  • 본 연구는 한우의 자궁내막염에서 발현 변화를 보이는 유전자를 마이크로어레이를 이용하여 조사하였다. 정상적인 자궁내막과 자궁내막염이 있는 자궁내막을 비교한 결과, 전체 확인된 4,560개의 유전자 중 2,026개의 유전자가 자궁내막염에서 증가하였고, 2,534개의 유전자가 감소하였다. 본 연구에서는 상위 조절되는 유전자 10개씩을 정리하였다. 자궁내막염에서 filamin A, pancreatic anionic trypsinogen, Rho GDP dissociation inhibitor alpha, collagen type VI alpha 1, butyrate response factor 2, aggrecanses-2, annexin 14, aminopeptidease A, orphan transporter v7-3 및 epithelial stromal interaction 1의 발현율이 $2^6$배 이상 증가하였다. MHC class II antigen, integrin-binding sialoprotein, uterine milk protein precursor, down-regulated in colon cancer 1, glycoprotein 330, dickkopf-1, cfh protein, $Ca^{2+}-dependent$ secretion activator, UL16 binding protein 3 및 proenkephalin은 $2^{5.5}$배 이상 감소하였다. 본 연구에서 얻어진 유전자 정보는 한우의 자궁내막염 진단에 필요한 유용한 생물지표로 사용되어질 수 있을 것으로 사료된다.

Induction of Neuron-derived Orphan Receptor-1 in the Dentate Gyrus of the Hippocampal Formation Following Transient Global Ischemia in the Rat

  • Kim, Younghwa;Hong, Soontaek;Noh, Mi Ra;Kim, Soo Young;Huh, Pil Woo;Park, Sun-Hwa;Sun, Woong;Kim, Hyun
    • Molecules and Cells
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    • 제22권1호
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    • pp.8-12
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    • 2006
  • Neuron-derived orphan receptor (NOR-1) is a member of the thyroid/steroid receptor superfamily that was originally identified in forebrain neuronal cells undergoing apoptosis. In addition to apoptotic stimuli, activation of several signal transduction pathways including direct neuronal depolarization regulates the expression of NOR-1. In this study we tested whether the expression of NOR-1 is changed following transient ischemic injury in the adult rat brain. NOR-1 mRNA increased rapidly in the dentate gyrus of the hippocampal formation and piriform cortex 3 h after transient global ischemia and returned to basal level at 6 h. On the other hand, oxygen-glucose deprivation of cultured cerebral cortical neurons did not alter the expression of NOR-1. These results suggest that expression of NOR-1 is differentially regulated in different brain regions in response to globally applied brain ischemia, but that hypoxia is not sufficient to induce its expression.

Constitutive androstane receptor (CAR)의 전사활성 저해제로서의 T0901317 (T0901317 as an Inhibitor of Transcriptional Activation of Constitutive Androstane Receptor (CAR))

  • 김현하;설원기
    • 생명과학회지
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    • 제21권4호
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    • pp.481-485
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    • 2011
  • T0901317은 핵수용체 전사인자인 liver X receptor (LXR, NR1H2/3)의 강력한 합성 리간드이다. 그러나, T0901317은 farnesoid X receptor (FXR, NR1H4)와 pregnane X receptor (PXR, NR1I2)에 대해 작용물질(agonist) 로, androgen receptor (AR, NR3C4)와 rertinoid-related orphan receptor-${\alpha}$ (ROR-${\alpha}$, NR1F1)에 대해 길항제(antagonist)로 작용하여, LXR외에 적어도 다른 4종의 핵수용체에 대해 그 활성을 조절한다고 보고되었다. 우리는 T0901317이 또 다른 핵수용체인 constitutive androstane receptor (CAR, NR1I3)에 대해 저해제로 기능함을 확인 하였다. CAR는 이미 T0901317에 의해 기능이 조절된다고 알려진 PXR, FXR, LXR과 더불어 간에서 생체이물과 콜레스테롤의 대사작용에 중요한 역할을 하므로 T0901317에 의해 CAR의 활성이 조절된다는 사실은, 간세포에서 T0901317을 이용한 실험 결과를 해석할 때 세포 내에 이미 존재하는 이들 핵수용체 단백질의 영향을 고려하여 주의깊게 해석해야 함을 의미한다.

Bisphenol A Bis(2,3-dihydroxypropyl) ether (BADGE.2H2O) Induces Orphan Nuclear Receptor Nur77 Gene Expression and Increases Steroidogenesis in Mouse Testicular Leydig Cells

  • Ahn, Seung-Won;Nedumaran, Balachandar;Xie, Yuanbin;Kim, Don-Kyu;Kim, Yong Deuk;Choi, Hueng-Sik
    • Molecules and Cells
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    • 제26권1호
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    • pp.74-80
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    • 2008
  • Bisphenol A bis (2,3-dihydroxypropyl) ether ($BADGE.2H_2O$) is a component of commercial liquid epoxy resins commonly used in the food-packing industry and in dental sealants. There is evidence that it has significant estrogenic activity. Nur77 plays a crucial role in the regulation of certain genes involved in LH-mediated steroidogenesis in testicular Leydig cells. It was previously demonstrated that Bisphenol A (BPA) stimulates Nur77 gene induction and steroidogenesis. In this study, we investigated the effects of $BADGE.2H_2O$ on Nur77 gene expression and steroidogenesis. Northern blot analysis showed that it increased the expression of Nur77 mRNA and protein, and transient transfection assays demonstrated that it increased the promoter activity and transactivation of Nur77. It also increased the expression of certain steroidogenic genes, such as StAR and $3{\beta}$-HSD. Finally, over-expression of a dominant negative Nur77 cDNA via adenoviral infection reduced $BADGE.2H_2O$-mediated progesterone biosynthesis. These results indicate that $BADGE.2H_2O$ disrupts testicular steroidogenesis by increasing Nur77 gene expression.

RORA 유전자 다형성과 한국인 젊은 성인에서 일중선호도와의 연관성 (Association of the RORA Gene Polymorphism and Diurnal Preference in a Young Korean Population)

  • 주훈;조철현;문정호;김린;이헌정
    • 수면정신생리
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    • 제23권1호
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    • pp.25-28
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    • 2016
  • 목 적 : Retinoid-related orphan receptor A (RORA) 유전자가 일주기리듬의 조절에 영향을 미친다는 사실이 알려져 왔다. 본 연구에서는 RORA 유전자다형성과 일중선호도의 연관성을 한국인 젊은 성인을 대상으로 분석하였다. 방 법 : 광고를 통해 모집한 504명의 젊은 성인이 최종적으로 대상에 포함되었다. 모든 대상은 13문항 composite scale for morningness (CSM)를 작성하였다. RORA rs11071547 단일염기다형성은 PCR 기반한 실험 방법을 통하여 분석하였다. 결 과 : CSM 점수결과 일중선호도는 RORA rs11071547 SNP의 유전자형과 대립유전자 보유여부에 따라 차이를 보이지 않았다. 결 론 : 이러한 연구결과는 RORA rs11071547 SNP가 일중선호도에 중요한 역할을 하지 않을 가능성을 보여준다.

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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    • 제47권2호
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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.