Particular phosphorylation of PI3K/Akt on Thr308 via PDK-1 and PTEN mediates melatonin's neuroprotective activity after focal cerebral ischemia in mice

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dc.authorid0000-0002-6895-8560
dc.authorid0000-0002-6242-3709
dc.authorid0000-0002-9476-8488
dc.authorid0000-0001-7702-2441
dc.authorid0000-0002-5072-132X
dc.authorid0000-0002-1064-7989
dc.authorid0000-0003-3616-1204
dc.authorid0000-0002-9704-6173
dc.authorid0000-0003-1106-3288
dc.authorid0000-0001-6494-8923
dc.contributor.authorKılıç, Ülkan
dc.contributor.authorÇağlayan, Ahmet Burak
dc.contributor.authorBeker, Mustafa Çağlar
dc.contributor.authorGünal, Mehmet Yalçın
dc.contributor.authorÇağlayan, Berrak
dc.contributor.authorYalçın, Esra
dc.contributor.authorKeleştemur, Taha
dc.contributor.authorGündoğdu, Reyhan Zeynep
dc.contributor.authorYuluğ, Burak
dc.contributor.authorYılmaz, Bayram
dc.contributor.authorKerman, Bilal Ersen
dc.contributor.authorKılıç, Ertuğrul
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T20:02:49Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T20:02:49Z
dc.date.issued2017
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Nöroloji Ana Bilim Dalı
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Histoloji ve Embriyoloji Ana Bilim Dalı
dc.descriptionWOS: 000403328700061
dc.descriptionPubMed ID: 28395173
dc.description.abstractApart from its potent antioxidant property, recent studies have revealed that melatonin promotes PI3K/Akt phosphorylation following focal cerebral ischemia (FCI) in mice. However, it is not clear (i) whether increased PI3K/Akt phosphorylation is a concomitant event or it directly contributes to melatonin's neuroprotective effect, and (ii) how melatonin regulates PI3K/Akt signaling pathway after FCI. In this study, we showed that Akt was intensively phosphorylated at the Thr308 activation loop as compared with Ser473 by melatonin after FCI. Melatonin treatment reduced infarct volume, which was reversed by PI3K/Akt inhibition. However, PI3K/Akt inhibition did not inhibit melatonin's positive effect on brain swelling and IgG extravasation. Additionally, phosphorylation of mTOR, PTEN, AMPK alpha, PDK1 and RSK1 were increased, while phosphorylation of 4E-BP1, GSK-3 alpha/beta, S6 ribosomal protein were decreased in melatonin treated animals. In addition, melatonin decreased apoptosis through reduced p53 phosphorylation by the PI3K/Akt pathway. In conclusion, we demonstrated the activation profiles of PI3K/Akt signaling pathway components in the pathophysiological aspect of ischemic stroke and melatonin's neuroprotective activity. Our data suggest that Akt phosphorylation, preferably at the Thr308 site of the activation loop via PDK1 and PTEN, mediates melatonin's neuroprotective activity and increased Akt phosphorylation leads to reduced apoptosis.
dc.description.sponsorshipTurkish Academy of Sciences (TUBA), Istanbul Medipol University; Bezmialem Vakif University Scientific Research Project Committeeen_US
dc.description.sponsorshipThis work was supported by The Turkish Academy of Sciences (TUBA), Istanbul Medipol University and Bezmialem Vakif University Scientific Research Project Committee.en_US
dc.identifier.citationKılıç, Ü., Çağlayan, A. B., Beker, M. Ç., Günal, M. Y., Çağlayan, B., Yalçın, E. ... Kılıç, E. (2017). Particular phosphorylation of PI3K/Akt on Thr308 via PDK-1 and PTEN mediates melatonin's neuroprotective activity after focal cerebral ischemia in mice. Redox Biology, 12, 657-665. https://dx.doi.org/10.1016/j.redox.2017.04.006
dc.identifier.doi10.1016/j.redox.2017.04.006
dc.identifier.endpage665
dc.identifier.issn2213-2317
dc.identifier.scopusqualityQ1
dc.identifier.startpage657
dc.identifier.urihttps://dx.doi.org/10.1016/j.redox.2017.04.006
dc.identifier.urihttps://hdl.handle.net/20.500.12511/3742
dc.identifier.volume12
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier Sciences Bv
dc.relation.ispartofRedox Biologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectPI3K/Akt Signaling Pathway
dc.subjectPI3K Inhibition
dc.subjectMelatonin
dc.subjectBrain Injury
dc.titleParticular phosphorylation of PI3K/Akt on Thr308 via PDK-1 and PTEN mediates melatonin's neuroprotective activity after focal cerebral ischemia in mice
dc.typeArticle

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