Time-of-day dependent neuronal injury after ischemic stroke: Implication of circadian clock transcriptional factor bmal1 and survival kinase akt

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dc.authorid0000-0002-9476-8488
dc.authorid0000-0002-5072-132X
dc.authorid0000-0002-1064-7989
dc.authorid0000-0002-6242-3709
dc.authorid0000-0003-3616-1204
dc.authorid0000-0002-6895-8560
dc.authorid0000-0001-6494-8923
dc.contributor.authorBeker, Mustafa Çağlar
dc.contributor.authorÇağlayan, Berrak
dc.contributor.authorYalçın, Esra
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorTürkseven, Şeyma
dc.contributor.authorGürel, Büşra
dc.contributor.authorKeleştemur, Taha
dc.contributor.authorSertel, Elif
dc.contributor.authorŞahin, Zafer
dc.contributor.authorKutlu, Selim
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorBaykal, Ahmet Tarık
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:50:47Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:50:47Z
dc.date.issued2018
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.descriptionWOS: 000426897800060
dc.descriptionPubMed ID: 28421530
dc.description.abstractOccurrence of stroke cases displays a time-of-day variation in human. However, the mechanism linking circadian rhythm to the internal response mechanisms against pathophysiological events after ischemic stroke remained largely unknown. To this end, temporal changes in the susceptibility to ischemia/reperfusion (I/R) injury were investigated in mice in which the ischemic stroke induced at four different Zeitgeber time points with 6-h intervals (ZT0, ZT6, ZT12, and ZT18). Besides infarct volume and brain swelling, neuronal survival, apoptosis, ischemia, and circadian rhythm related proteins were examined using immunohistochemistry, Western blot, planar surface immune assay, and liquid chromatography-mass spectrometry tools. Here, we present evidence that midnight (ZT18; 24:00) I/R injury in mice resulted in significantly improved infarct volume, brain swelling, neurological deficit score, neuronal survival, and decreased apoptotic cell death compared with ischemia induced at other time points, which were associated with increased expressions of circadian proteins Bmal1, PerI, and Clock proteins and survival kinases AKT and Erk-1/2. Moreover, ribosomal protein S6, mTOR, and Bad were also significantly increased, while the levels of PRAS40, negative regulator of AKT and mTOR, and phosphorylated p53 were decreased at this time point compared to ZT0 (06:00). Furthermore, detailed proteomic analysis revealed significantly decreased CSKP, HBB-1/2, and HBA levels, while increased GNAZ, NEGR1, IMPCT, and PDE1B at midnight as compared with early morning. Our results indicate that nighttime I/R injury results in less severe neuronal damage, with increased neuronal survival, increased levels of survival kinases and circadian clock proteins, and also alters the circadian-related proteins.
dc.description.sponsorshipNecmettin Erbakan University [161330001]; Turkish Academy of Sciences (TUBA)en_US
dc.description.sponsorshipThis study was supported by The Turkish Academy of Sciences (TUBA) and Necmettin Erbakan University (Scientific Research Project: 161330001).en_US
dc.identifier.citationBeker, M. Ç., Çağlayan, B., Yalçın, E., Çağlayan, A. B., Türkseven, Ş., Gürel, B. … Kılıç, E. (2018). Time-of-day dependent neuronal injury after ischemic stroke: Implication of circadian clock transcriptional factor bmal1 and survival kinase akt. Molecular Neurobiology, 55(3), 2565-2576. https://dx.doi.org/10.1007/s12035-017-0524-4
dc.identifier.doi10.1007/s12035-017-0524-4
dc.identifier.endpage2576
dc.identifier.issn0893-7648
dc.identifier.issn1559-1182
dc.identifier.issue3
dc.identifier.scopusqualityQ1
dc.identifier.startpage2565
dc.identifier.urihttps://dx.doi.org/10.1007/s12035-017-0524-4
dc.identifier.urihttps://hdl.handle.net/20.500.12511/2076
dc.identifier.volume55
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherHumana Press Inc
dc.relation.ispartofMolecular Neurobiologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectCircadian Rhythm
dc.subjectCerebral Ischemia
dc.subjectProteomics
dc.subjectAkt Signaling
dc.subjectPI3K
dc.subjectBmal1
dc.titleTime-of-day dependent neuronal injury after ischemic stroke: Implication of circadian clock transcriptional factor bmal1 and survival kinase akt
dc.typeArticle

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