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dc.contributor.authorMathew, Divya Elizabeth
dc.contributor.authorLarsen, Kaitlyn
dc.contributor.authorJaneczek, Paulina
dc.contributor.authorLewohl, Joanne M
dc.date.accessioned2019-03-12T01:18:20Z
dc.date.available2019-03-12T01:18:20Z
dc.date.issued2016
dc.identifier.issn1044-7431
dc.identifier.doi10.1016/j.mcn.2016.06.006
dc.identifier.urihttp://hdl.handle.net/10072/142450
dc.description.abstractThe 14-3-3 proteins are a family of highly conserved molecular chaperones involved in the regulation of a number of key cellular functions including metabolism, stress response, protein trafficking, cell-cycle control, signal transduction, transcription, apoptosis and neurotransmission. 14-3-3 proteins have also been implicated in the pathophysiology of neurodegenerative disorders including Alzheimer disease and Parkinson disease. Recent studies have also shown that 14-3-3s are differentially expressed in the frontal cortex of human alcoholics suggesting a potential role in the pathophysiology of alcohol use disorders. Here we measured the expression of 14-3-3 transcripts in HEK293T cells in response to chronic ethanol treatment. Five of the seven transcripts (14-3-3β, 14-3-3γ, 14-3-3ζ, 14-3-3ε and 14-3-3θ) were significantly down-regulated following chronic exposure to ethanol for a five day period with these changes persisting even after withdrawal from ethanol treatment. One transcript, 14-3-3σ, was significantly up-regulated following chronic ethanol exposure and 14-3-3η showed no differences in expression in the same treatment model. The pattern of expression changes is similar to those seen in the frontal cortex of human alcoholics. To investigate the role of miRNAs in mediating the expression changes we measured the expression of the 14-3-3 transcripts following transfection with miR-203, miR-144 and miR-7 mimics. Although these miRNAs had predicted target sites in the 3’untranslated region of each 14-3-3 isoform, only miR-203 resulted in a down-regulation of 14-3-3θ transcript. In addition, the expression of 14-3-3γ was upregulated following transfection with miR-7 and miR-144 mimics. MiRNA regulation of these isoforms following alcohol exposure may lead to alterations in neurotransmission, the balance between cell survival and cell death, as well as changing the rewarding effects of alcohol.
dc.description.peerreviewedYes
dc.languageEnglish
dc.publisherElsevier
dc.relation.ispartofpagefrom44
dc.relation.ispartofpageto49
dc.relation.ispartofjournalMolecular and Cellular Neuroscience
dc.relation.ispartofvolume75
dc.subject.fieldofresearchNeurosciences not elsewhere classified
dc.subject.fieldofresearchNeurosciences
dc.subject.fieldofresearchPsychology
dc.subject.fieldofresearchCognitive Sciences
dc.subject.fieldofresearchcode110999
dc.subject.fieldofresearchcode1109
dc.subject.fieldofresearchcode1701
dc.subject.fieldofresearchcode1702
dc.titleExpression of 14-3-3 transcript isoforms in response to ethanol exposure and their regulation by miRNAs
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/
gro.facultyGriffith Health, Menzies Health Institute
gro.hasfulltextNo Full Text
gro.griffith.authorLewohl, Joanne M.
gro.griffith.authorJaneczek, Paulina
gro.griffith.authorLarsen, Kaitlyn J.
gro.griffith.authorMathew, Divya Elizabeth E.


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