Identification of differentially expressed microRNAs during lipotoxic endoplasmic reticulum stress in RAW264.7 macrophages

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dc.citation.epage215en_US
dc.citation.issueNumber3en_US
dc.citation.spage206en_US
dc.citation.volumeNumber41en_US
dc.contributor.authorNadir, M.en_US
dc.contributor.authorTufanlı, Ö.en_US
dc.contributor.authorErbay, E.en_US
dc.contributor.authorAtalay, A.en_US
dc.date.accessioned2018-04-12T10:51:13Z
dc.date.available2018-04-12T10:51:13Z
dc.date.issued2016-06en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.description.abstractObjective: Increased fatty acids in the circulation and their accumulation in non-adipose tissues play a significant role in the development of obesity related metabolic and inflammatory disorders such as insulin resistance, diabetes and atherosclerosis. While fat tissue has the ability to store excess fatty acids, uptake of excess fatty acids to other tissues burdens intracellular metabolic organelles such as mitochondria and endoplasmic reticulum (ER), leading to stress response and lipotoxic cell death. Unfolded protein response (UPR) is a key adaptation of the ER to stress. It is still not completely clear how lipids engage the UPR and how UPR manages both the adaptive and destructive consequences under its control. Increasing evidence point to the importance of miRNA regulation of the UPR as well as UPR’s role in miRNA biogenesis. In order to understand how lipids engage the UPR, we set forth to identify microRNAs regulated by lipotoxic ER stress in macrophages. Methods: We stressed the mouse macrophage cell line (RAW 264.7) with a saturated fatty acid, 500μM palmitate, reflecting the levels found in the circulation of obese patients. We analyzed the microRNAome profiles of this cell line using QRT-PCR based miScript miRNA PCR array which contained all known mouse microRNAs in miRBase release16 and performed pathway analysis for potential targets. Results: 227 microRNAs showed altered expression levels; 43 microRNAs above 2 fold difference and 13 microRNAs 3-24 fold difference. Pathway analysis enriched the target mRNAs of these lipotoxic ER stress associated miRNAs. Conclusion: When exposed to high concentrations of saturated fatty acids that can induce ER stress, macrophages display a dynamic range of changes in their microRNAome profiles. Our findings reflect the consequences of lipotoxic stress on circulating monocytes and tissue-associated macrophages in obesity. Further studies are needed to deliniate which UPR arm is reponsible for the microRNA changes reported here.en_US
dc.description.provenanceMade available in DSpace on 2018-04-12T10:51:13Z (GMT). No. of bitstreams: 1 bilkent-research-paper.pdf: 179475 bytes, checksum: ea0bedeb05ac9ccfb983c327e155f0c2 (MD5) Previous issue date: 2016en
dc.identifier.doi10.1515/tjb-2016-0031en_US
dc.identifier.issn0250-4685
dc.identifier.urihttp://hdl.handle.net/11693/36731
dc.language.isoEnglishen_US
dc.publisherTurkish Biochemistry Societyen_US
dc.relation.isversionofhttps://doi.org/10.1515/tjb-2016-0031en_US
dc.source.titleTurkish Journal of Biochemistryen_US
dc.subjectLipotoxic endoplasmic reticulum stressen_US
dc.subjectMacrophageen_US
dc.subjectMicroRNAen_US
dc.subjectPathway analysisen_US
dc.subjectQRTPCRen_US
dc.subjectRAW264.7en_US
dc.subjectUnfolded protein responseen_US
dc.subjectMicroRNAen_US
dc.subjectSaturated fatty aciden_US
dc.subjectAdipose tissueen_US
dc.subjectAgar gel electrophoresisen_US
dc.subjectAnimal cellen_US
dc.subjectArticleen_US
dc.subjectAtherosclerosisen_US
dc.subjectBiosynthesisen_US
dc.subjectCell deathen_US
dc.subjectCell differentiationen_US
dc.subjectControlled studyen_US
dc.subjectDiabetes mellitusen_US
dc.subjectDNA synthesisen_US
dc.subjectDown regulationen_US
dc.subjectEndoplasmic reticulum stressen_US
dc.subjectGene expressionen_US
dc.subjectGene ontologyen_US
dc.subjectGenetic analysisen_US
dc.subjectHumanen_US
dc.subjectImmune responseen_US
dc.subjectImmunocompetent cellen_US
dc.subjectInsulin resistanceen_US
dc.subjectLipotoxicityen_US
dc.subjectMacrophageen_US
dc.subjectMouseen_US
dc.subjectNonhumanen_US
dc.subjectObesityen_US
dc.subjectProtein degradationen_US
dc.subjectProtein expressionen_US
dc.subjectProtein foldingen_US
dc.subjectReverse transcription polymerase chain reactionen_US
dc.subjectRNA isolationen_US
dc.subjectUnfolded protein responseen_US
dc.titleIdentification of differentially expressed microRNAs during lipotoxic endoplasmic reticulum stress in RAW264.7 macrophagesen_US
dc.title.alternativeRAW264.7 makrofajlarında lipotoksik endoplazmik retikulum stres sürecinde ifadesi değişen mikroRNAların tanımlanmasıen_US
dc.typeArticleen_US

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