[논문]Nurr1 performs its anti-inflammatory function by regulating RasGRP1 expression in neuro-inflammation

Oh, Mihee; Kim, Sun Young; Gil, Jung-Eun; Byun, Jeong-Su; Cha, Dong-Wook; Ku, Bonsu; Lee, Woonghee; Kim, Won-Kon; Oh, Kyoung-Jin; Lee, Eun-Woo; Bae, Kwang-Hee; Lee, Sang Chul; Han, Baek-Soo

doi:10.1038/s41598-020-67549-7

[해외논문] Nurr1 performs its anti-inflammatory function by regulating RasGRP1 expression in neuro-inflammation 원문보기

Scientific reports, v.10, 2020년, pp.10755 -

Oh, Mihee (Biodefense Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Republic of Korea) , Kim, Sun Young (Biodefense Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Republic of Korea) , Gil, Jung-Eun (Biodefense Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Republic of Korea) , Byun, Jeong-Su (Biodefense Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Republic of Korea) , Cha, Dong-Wook (Biodefense Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Republic of Korea) , Ku, Bonsu (Disease Target Structure Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Republic of Korea) , Lee, Woonghee (MODNBIO Inc., Seoul, 08378 Republic of Korea) , Kim, Won-Kon (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141 Republic of Korea) , Oh, Kyoung-Jin (Metabolic Regulation Research Center, Korea Research Institute of Bioscience and B) , Lee, Eun-Woo , Bae, Kwang-Hee , Lee, Sang Chul , Han, Baek-Soo

Abstract ▼ AI-Helper

Nurr1, a transcription factor belonging to the orphan nuclear receptor, has an essential role in the generation and maintenance of dopaminergic neurons and is important in the pathogenesis of Parkinson’ disease (PD). In addition, Nurr1 has a non-neuronal function, and it is especially well known that Nurr1 has an anti-inflammatory function in the Parkinson’s disease model. However, the molecular mechanisms of Nurr1 have not been elucidated. In this study, we describe a novel mechanism of Nurr1 function. To provide new insights into the molecular mechanisms of Nurr1 in the inflammatory response, we performed Chromatin immunoprecipitation sequencing (ChIP-Seq) on LPS-induced inflammation in BV2 cells and finally identified the RasGRP1 gene as a novel target of Nurr1. Here, we show that Nurr1 directly binds to the RasGRP1 intron to regulate its expression. Moreover, we also identified that RasGRP1 regulates the Ras-Raf-MEK-ERK signaling cascade in LPS-induced inflammation signaling. Finally, we conclude that RasGRP1 is a novel regulator of Nurr1’s mediated inflammation signaling.

참고문헌 (67)

1. Perlmann T Wallen-Mackenzie A Nurr1, an orphan nuclear receptor with essential functions in developing dopamine cells Cell Tissue Res 2004 318 45 52 10.1007/s00441-004-0974-7 15340833

상세보기
2. Mazaira GI The nuclear receptor field: A historical overview and future challenges Nucl. Receptor Res. 2018 10.11131/2018/101320 30148160

상세보기
3. Giguere V Orphan nuclear receptors: from gene to function Endocr. Rev. 1999 20 689 725 10.1210/edrv.20.5.0378 10529899

상세보기
4. Kim KS Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell-specific manner J Neurochem 2003 85 622 634 10.1046/j.1471-4159.2003.01671.x 12694388

상세보기
5. Wallen AA Orphan nuclear receptor Nurr1 is essential for Ret expression in midbrain dopamine neurons and in the brain stem Mol. Cell. Neurosci. 2001 18 649 663 10.1006/mcne.2001.1057 11749040

상세보기
6. Decressac M Volakakis N Bjorklund A Perlmann T NURR1 in Parkinson disease from pathogenesis to therapeutic potential Nat. Rev. Neurol. 2013 9 629 636 10.1038/nrneurol.2013.209 24126627

상세보기
7. Le WD Mutations in NR4A2 associated with familial Parkinson disease Nat. Genet. 2003 33 85 89 10.1038/ng1066 12496759

상세보기
8. Kim T In vitro generation of mature midbrain-type dopamine neurons by adjusting exogenous Nurr1 and Foxa2 expressions to their physiologic patterns Exp. Mol. Med. 2017 49 e300 10.1038/emm.2016.163 28280264

상세보기
9. Chen XX Nurr1 promotes neurogenesis of dopaminergic neuron and represses inflammatory factors in the transwell coculture system of neural stem cells and microglia CNS Neurosci. Ther. 2018 24 790 800 10.1111/cns.12825 29450981

상세보기
10. Wang X The lentiviral-mediated Nurr1 genetic engineering mesenchymal stem cells protect dopaminergic neurons in a rat model of Parkinson's disease Am. J. Transl. Res. 2018 10 1583 1599 30018702
11. Salemi S Efficient generation of dopaminergic-like neurons by overexpression of Nurr1 and Pitx3 in mouse induced pluripotent stem cells Neurosci. Lett. 2016 626 126 134 10.1016/j.neulet.2016.05.032 27208834

상세보기
12. Saijo K A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death Cell 2009 137 47 59 10.1016/j.cell.2009.01.038 19345186

상세보기
13. Tjalkens RB Popichak KA Kirkley KA Inflammatory activation of microglia and astrocytes in manganese neurotoxicity Adv. Neurobiol. 2017 18 159 181 10.1007/978-3-319-60189-2_8 28889267
14. Barbierato M Astrocyte-microglia cooperation in the expression of a pro-inflammatory phenotype CNS Neurol. Disord. Drug Targets 2013 12 608 618 10.2174/18715273113129990064 23574172

상세보기
15. Kano SI Glutathione S-transferases promote proinflammatory astrocyte-microglia communication during brain inflammation Sci. Signal. 2019 10.1126/scisignal.aar2124 30783009

상세보기
16. Barish GD A nuclear receptor atlas: Macrophage activation Mol. Endocrinol. 2005 19 2466 2477 10.1210/me.2004-0529 16051664

상세보기
17. Pei L Castrillo A Chen M Hoffmann A Tontonoz P Induction of NR4A orphan nuclear receptor expression in macrophages in response to inflammatory stimuli J. Biol. Chem. 2005 280 29256 29262 10.1074/jbc.M502606200 15964844

상세보기
18. Bonta PI Nuclear receptors Nur77, Nurr1, and NOR-1 expressed in atherosclerotic lesion macrophages reduce lipid loading and inflammatory responses Arterioscler. Thromb. Vasc. Biol. 2006 26 2288 2294 10.1161/01.ATV.0000238346.84458.5d 16873729

상세보기
19. Montarolo F Martire S Perga S Bertolotto A NURR1 impairment in multiple sclerosis Int. J. Mol. Sci. 2019 10.3390/ijms20194858 31574937

상세보기
20. Liu H Decreased NURR1 and PITX3 gene expression in Chinese patients with Parkinson's disease Eur. J. Neurol. 2012 19 870 875 10.1111/j.1468-1331.2011.03644.x 22309633

상세보기
21. Kim CH Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson's disease Proc. Natl. Acad. Sci. USA 2015 112 8756 8761 10.1073/pnas.1509742112 26124091

상세보기
22. Smith GA A Nurr1 agonist causes neuroprotection in a Parkinson's disease lesion model primed with the toll-like receptor 3 dsRNA inflammatory stimulant poly(I:C) PLoS ONE 2015 10 e0121072 10.1371/journal.pone.0121072 25815475

상세보기
23. Liu W Gao Y Chang N Nurr1 overexpression exerts neuroprotective and anti-inflammatory roles via down-regulating CCL2 expression in both in vivo and in vitro Parkinson's disease models Biochem. Biophys. Res. Commun. 2017 482 1312 1319 10.1016/j.bbrc.2016.12.034 27940361

상세보기
24. Jodeiri Farshbaf M Nurr1 and PPARgamma protect PC12 cells against MPP(+) toxicity: involvement of selective genes, anti-inflammatory, ROS generation, and antimitochondrial impairment Mol. Cell. Biochem. 2016 420 29 42 10.1007/s11010-016-2764-4 27435855

상세보기
25. Zetterstrom RH Williams R Perlmann T Olson L Cellular expression of the immediate early transcription factors Nurr1 and NGFI-B suggests a gene regulatory role in several brain regions including the nigrostriatal dopamine system Brain Res. Mol. Brain Res. 1996 41 111 120 10.1016/0169-328X(96)00074-5 8883941

상세보기
26. Streit WJ Microglia and macrophages in the developing CNS Neurotoxicology 2001 22 619 624 10.1016/s0161-813x(01)00033-x 11770883

상세보기
27. Yang I Han SJ Kaur G Crane C Parsa AT The role of microglia in central nervous system immunity and glioma immunology J. Clin. Neurosci. 2010 17 6 10 10.1016/j.jocn.2009.05.006 19926287

상세보기
28. Stansley B Post J Hensley K A comparative review of cell culture systems for the study of microglial biology in Alzheimer's disease J. Neuroinflamm. 2012 9 115 10.1186/1742-2094-9-115

상세보기
29. Henn A The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation Altex 2009 26 83 94 10.14573/altex.2009.2.83 19565166

상세보기
30. Roy J Primary microglia isolation from mixed cell cultures of neonatal mouse brain tissue Brain Res. 2018 1689 21 29 10.1016/j.brainres.2018.03.018 29577885

상세보기
31. Roy J Retraction notice to "primary microglia isolation from mixed cell cultures of neonatal mouse brain tissue" [Brain Res. 1689 (2018) 21？29] Brain Res. 2018 1699 195 10.1016/j.brainres.2018.08.017 30340653

상세보기
32. Tamashiro TT Dalgard CL Byrnes KR Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue J. Vis. Exp. 2012 10.3791/3814 22929966

상세보기
33. Ni M Aschner M Neonatal rat primary microglia: isolation, culturing, and selected applications Curr. Protoc. Toxicol. 2010 10.1002/0471140856.tx1217s43 20960423

상세보기
34. Zhang Y Model-based analysis of ChIP-Seq (MACS) Genome Biol. 2008 9 R137 10.1186/gb-2008-9-9-r137 18798982

상세보기
35. Liu T Use model-based analysis of ChIP-Seq (MACS) to analyze short reads generated by sequencing protein？DNA interactions in embryonic stem cells Methods Mol. Biol. 2014 1150 81 95 10.1007/978-1-4939-0512-6_4 24743991

상세보기
36. Ji H An integrated software system for analyzing ChIP-chip and ChIP-seq data Nat. Biotechnol. 2008 26 1293 1300 10.1038/nbt.1505 18978777

상세보기
37. Kharchenko PV Tolstorukov MY Park PJ Design and analysis of ChIP-seq experiments for DNA-binding proteins Nat. Biotechnol. 2008 26 1351 1359 10.1038/nbt.1508 19029915

상세보기
38. Portales-Casamar E JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles Nucleic Acids Res. 2010 38 D105 110 10.1093/nar/gkp950 19906716

상세보기
39. Mahony S Benos PV STAMP: a web tool for exploring DNA-binding motif similarities Nucleic Acids Res. 2007 35 W253 258 10.1093/nar/gkm272 17478497

상세보기
40. Visel A ChIP-seq accurately predicts tissue-specific activity of enhancers Nature 2009 457 854 858 10.1038/nature07730 19212405

상세보기
41. Chang F Signal transduction mediated by the Ras/Raf/MEK/ERK pathway from cytokine receptors to transcription factors: potential targeting for therapeutic intervention Leukemia 2003 17 1263 1293 10.1038/sj.leu.2402945 12835716

상세보기
42. Reynolds LF Vav1 transduces T cell receptor signals to the activation of the Ras/ERK pathway via LAT, Sos, and RasGRP1 J. Biol. Chem. 2004 279 18239 18246 10.1074/jbc.M400257200 14764585

상세보기
43. Scheffzek K Shivalingaiah G Ras-specific GTPase-activating proteins-structures, mechanisms, and interactions Cold Spring Harb. Perspect. Med. 2018 10.1101/cshperspect.a031500

상세보기
44. Tazmini G Membrane localization of RasGRP1 is controlled by an EF-hand, and by the GEF domain Biochim. Biophys. Acta 2009 1793 447 461 10.1016/j.bbamcr.2008.12.019 19168098

상세보기
45. Coughlin JJ Stang SL Dower NA Stone JC RasGRP1 and RasGRP3 regulate B cell proliferation by facilitating B cell receptor-Ras signaling J. Immunol. 2005 175 7179 7184 10.4049/jimmunol.175.11.7179 16301621

상세보기
46. Hoffmann C A novel SP1/SP3 dependent intronic enhancer governing transcription of the UCP3 gene in brown adipocytes PLoS ONE 2013 8 e83426 10.1371/journal.pone.0083426 24391766

상세보기
47. Khandekar M A Gata2 intronic enhancer confers its pan-endothelia-specific regulation Development 2007 134 1703 1712 10.1242/dev.001297 17395646

상세보기
48. Pattison JM Posternak V Cole MD Transcription factor KLF5 binds a cyclin E1 polymorphic intronic enhancer to confer increased bladder cancer risk Mol. Cancer Res. 2016 14 1078 1086 10.1158/1541-7786.MCR-16-0123 27514407

상세보기
49. Nagpal K Watanabe KS Tsao BP Tsokos GC Transcription factor Ikaros represses protein phosphatase 2A (PP2A) expression through an intronic binding site J. Biol. Chem. 2014 289 13751 13757 10.1074/jbc.M114.558197 24692537

상세보기
50. Fontemaggi G The transcriptional repressor ZEB regulates p73 expression at the crossroad between proliferation and differentiation Mol. Cell. Biol. 2001 21 8461 8470 10.1128/MCB.21.24.8461-8470.2001 11713281

상세보기
51. Sacchetti P Mitchell TR Granneman JG Bannon MJ Nurr1 enhances transcription of the human dopamine transporter gene through a novel mechanism J. Neurochem. 2001 76 1565 1572 10.1046/j.1471-4159.2001.00181.x 11238740

상세보기
52. Gray S Levine M Transcriptional repression in development Curr. Opin. Cell. Biol. 1996 8 358 364 10.1016/S0955-0674(96)80010-X 8743887

상세보기
53. Nissen RM Yamamoto KR The glucocorticoid receptor inhibits NFkappaB by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain Genes Dev. 2000 14 2314 2329 10.1101/gad.827900 10995388

상세보기
54. Deckert J Struhl K Targeted recruitment of Rpd3 histone deacetylase represses transcription by inhibiting recruitment of Swi/Snf, SAGA, and TATA binding protein Mol. Cell. Biol. 2002 22 6458 6470 10.1128/MCB.22.18.6458-6470.2002 12192044

상세보기
55. Nibu Y Senger K Levine M CtBP-independent repression in the Drosophila embryo Mol. Cell. Biol. 2003 23 3990 3999 10.1128/MCB.23.11.3990-3999.2003 12748300

상세보기
56. Zhong J RAS and downstream RAF-MEK and PI3K-AKT signaling in neuronal development, function and dysfunction Biol. Chem. 2016 397 215 222 10.1515/hsz-2015-0270 26760308

상세보기
57. Marshall CJ Specificity of receptor tyrosine kinase signaling: transient versus sustained extracellular signal-regulated kinase activation Cell 1995 80 179 185 10.1016/0092-8674(95)90401-8 7834738

상세보기
58. Depeille P Roose JP Flavors of EGFR-Ras signals impacting intestinal homeostasis Cell Cycle 2015 14 3205 3206 10.1080/15384101.2015.1084203 26292152

상세보기
59. Zahedi B Phosphoinositide 3-kinase regulates plasma membrane targeting of the Ras-specific exchange factor RasGRP1 J. Biol. Chem. 2011 286 12712 12723 10.1074/jbc.M110.189605 21285350

상세보기
60. Roose JP Mollenauer M Gupta VA Stone J Weiss A A diacylglycerol-protein kinase C-RasGRP1 pathway directs Ras activation upon antigen receptor stimulation of T cells Mol. Cell. Biol. 2005 25 4426 4441 10.1128/MCB.25.11.4426-4441.2005 15899849

상세보기
61. Platt CD Combined immunodeficiency with EBV positive B cell lymphoma and epidermodysplasia verruciformis due to a novel homozygous mutation in RASGRP1 Clin. Immunol. 2017 183 142 144 10.1016/j.clim.2017.08.007 28822832

상세보기
62. Huang H The RAS guanyl nucleotide-releasing protein RasGRP1 is involved in lymphatic development in zebrafish J. Biol. Chem. 2013 288 2355 2364 10.1074/jbc.M112.418202 23184941

상세보기
63. Shahani N RasGRP1 promotes amphetamine-induced motor behavior through a Rhes interaction network ("Rhesactome") in the striatum Sci. Signal. 2016 9 ra111 10.1126/scisignal.aaf6670 27902448

상세보기
64. Jo H Hindsiipropane B alleviates HIV-1 Tat-induced inflammatory responses by suppressing HDAC6-NADPH oxidase-ROS axis in astrocytes BMB Rep. 2018 51 394 399 10.5483/bmbrep.2018.51.8.061 29699604

원문보기 상세보기
65. Codina A Identification of a novel co-regulator interaction surface on the ligand binding domain of Nurr1 using NMR footprinting J. Biol. Chem. 2004 279 53338 53345 10.1074/jbc.M409096200 15456745

상세보기
66. Carpentier R Sacchetti P Segard P Staels B Lefebvre P The glucocorticoid receptor is a co-regulator of the orphan nuclear receptor Nurr1 J. Neurochem. 2008 104 777 789 10.1111/j.1471-4159.2007.05055.x 17986226

상세보기
67. Wang J Nemo-like kinase as a negative regulator of nuclear receptor Nurr1 gene transcription in prostate cancer BMC Cancer 2016 16 257 10.1186/s12885-016-2291-4 27036119

상세보기

LOADING...

활용도 분석정보

상세보기

다운로드

내보내기

활용도 Top5 논문

해당 논문의 주제분야에서 활용도가 높은 상위 5개 콘텐츠를 보여줍니다.
더보기 버튼을 클릭하시면 더 많은 관련자료를 살펴볼 수 있습니다.

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증