Please use this identifier to cite or link to this item: https://hdl.handle.net/11147/5894
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dc.contributor.authorAlural, Begüm-
dc.contributor.authorÖzerdem, Ayşegül-
dc.contributor.authorAllmer, Jens-
dc.contributor.authorGenç, Kürşad-
dc.contributor.authorGenç, Şermin-
dc.date.accessioned2017-07-07T13:31:14Z-
dc.date.available2017-07-07T13:31:14Z-
dc.date.issued2015-05-28-
dc.identifier.citationAlural, B., Özerdem, A., Allmer, J., Genç, K., and Genç, S. (2015). Lithium protects against paraquat neurotoxicity by NRF2 activation and miR-34a inhibition in SH-SY5Y cells. Frontiers in Cellular Neuroscience, 9(MAY). doi:10.3389/fncel.2015.00209en_US
dc.identifier.issn1662-5102-
dc.identifier.urihttps://doi.org/10.3389/fncel.2015.00209-
dc.identifier.urihttp://hdl.handle.net/11147/5894-
dc.description.abstractLithium is a mood stabilizing agent commonly used for the treatment of bipolar disorder. Here, we investigated the potential neuroprotective effect of lithium against paraquat toxicity and its underlying mechanisms in vitro. SH-SY5Y human neuroblastoma cells were treated with paraquat (PQ) 0.5 mM concentration after lithium pretreatment to test lithium's capability in preventing cell toxicity. Cell death was evaluated by LDH, WST-8, and tryphan blue assays. Apoptosis was analyzed using DNA fragmentation, Annexin V immunostaining, Sub G1 cell cycle analysis, and caspase-3 activity assays. BCL2, BAX, and NRF2 protein expression were evaluated by Western-blotting and the BDNF protein level was determined with ELISA. mRNA levels of BCL2, BAX, BDNF, and NRF2 target genes (HO-1, GCS, NQO1), as well as miR-34a expression were analyzed by qPCR assay. Functional experiments were done via transfection with NRF2 siRNA and miR-34a mimic. Lithium treatment prevented paraquat induced cell death and apoptosis. Lithium treated cells showed increased anti-apoptotic protein BCL2 and decreased pro-apoptotic protein BAX expression. Lithium exerted a neurotrophic effect by increasing BDNF protein expression. It also diminished reactive oxygen species production and activated the redox sensitive transcription factor NRF2 and increased its target genes expression. Knockdown of NRF2 abolished neuroprotective, anti-apoptotic, and anti-oxidant effects of lithium. Furthermore, lithium significantly decreased both basal and PQ-induced expression of miR-34a. Transfection of miR-34a specific mimic reversed neuroprotective, anti-apoptotic, and anti-oxidant effects of lithium against PQ-toxicity. Our results revealed two novel mechanisms of lithium neuroprotection, namely NRF2 activation and miR-34a suppression.en_US
dc.description.sponsorshipScientific and Technological Research Council of Turkey (212T107)en_US
dc.language.isoenen_US
dc.publisherFrontiers Media S.A.en_US
dc.relation.ispartofFrontiers in Cellular Neuroscienceen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectNRF2en_US
dc.subjectBipolar disorderen_US
dc.subjectLithiumen_US
dc.subjectParkinson's diseaseen_US
dc.subjectCeramide glucosyltransferaseen_US
dc.titleLithium protects against paraquat neurotoxicity by NRF2 activation and miR-34a inhibition in SH-SY5Y cellsen_US
dc.typeArticleen_US
dc.authoridTR107974en_US
dc.institutionauthorAllmer, Jens-
dc.departmentİzmir Institute of Technology. Molecular Biology and Geneticsen_US
dc.identifier.volume9en_US
dc.identifier.issueMAYen_US
dc.identifier.wosWOS:000357523300001en_US
dc.identifier.scopus2-s2.0-84930665355en_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.doi10.3389/fncel.2015.00209-
dc.identifier.pmid26074776en_US
dc.relation.doi10.3389/fncel.2015.00209en_US
dc.coverage.doi10.3389/fncel.2015.00209en_US
dc.identifier.wosqualityQ1-
dc.identifier.scopusqualityQ1-
item.fulltextWith Fulltext-
item.openairetypeArticle-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.languageiso639-1en-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
crisitem.author.dept04.03. Department of Molecular Biology and Genetics-
Appears in Collections:Molecular Biology and Genetics / Moleküler Biyoloji ve Genetik
PubMed İndeksli Yayınlar Koleksiyonu / PubMed Indexed Publications Collection
Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
WoS İndeksli Yayınlar Koleksiyonu / WoS Indexed Publications Collection
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