dc.contributor.author | Kılıç, Ülkan | |
dc.contributor.author | Çağlayan, Ahmet Burak | |
dc.contributor.author | Beker, Mustafa Çağlar | |
dc.contributor.author | Günal, Mehmet Yalçın | |
dc.contributor.author | Çağlayan, Berrak | |
dc.contributor.author | Yalçın, Esra | |
dc.contributor.author | Keleştemur, Taha | |
dc.contributor.author | Gündoğdu, Reyhan Zeynep | |
dc.contributor.author | Yuluğ, Burak | |
dc.contributor.author | Yılmaz, Bayram | |
dc.contributor.author | Kerman, Bilal Ersen | |
dc.contributor.author | Kılıç, Ertuğrul | |
dc.date.accessioned | 10.07.201910:49:13 | |
dc.date.accessioned | 2019-07-10T20:02:49Z | |
dc.date.available | 10.07.201910:49:13 | |
dc.date.available | 2019-07-10T20:02:49Z | |
dc.date.issued | 2017 | en_US |
dc.identifier.citation | Kılıç, 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 | en_US |
dc.identifier.issn | 2213-2317 | |
dc.identifier.uri | https://dx.doi.org/10.1016/j.redox.2017.04.006 | |
dc.identifier.uri | https://hdl.handle.net/20.500.12511/3742 | |
dc.description | WOS: 000403328700061 | en_US |
dc.description | PubMed ID: 28395173 | en_US |
dc.description.abstract | Apart 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. | en_US |
dc.description.sponsorship | Turkish Academy of Sciences (TUBA), Istanbul Medipol University; Bezmialem Vakif University Scientific Research Project Committee | en_US |
dc.description.sponsorship | This work was supported by The Turkish Academy of Sciences (TUBA), Istanbul Medipol University and Bezmialem Vakif University Scientific Research Project Committee. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Elsevier Sciences Bv | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | PI3K/Akt Signaling Pathway | en_US |
dc.subject | PI3K Inhibition | en_US |
dc.subject | Melatonin | en_US |
dc.subject | Brain Injury | en_US |
dc.title | Particular phosphorylation of PI3K/Akt on Thr308 via PDK-1 and PTEN mediates melatonin's neuroprotective activity after focal cerebral ischemia in mice | en_US |
dc.type | article | en_US |
dc.relation.ispartof | Redox Biology | en_US |
dc.department | İstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER) | en_US |
dc.department | İstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı | en_US |
dc.department | İstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Fizyoloji Ana Bilim Dalı | en_US |
dc.department | İstanbul Medipol Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Nöroloji Ana Bilim Dalı | en_US |
dc.department | İstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Histoloji ve Embriyoloji Ana Bilim Dalı | en_US |
dc.authorid | 0000-0002-6895-8560 | en_US |
dc.authorid | 0000-0002-6242-3709 | en_US |
dc.authorid | 0000-0002-9476-8488 | en_US |
dc.authorid | 0000-0001-7702-2441 | en_US |
dc.authorid | 0000-0002-5072-132X | en_US |
dc.authorid | 0000-0002-1064-7989 | en_US |
dc.authorid | 0000-0003-3616-1204 | en_US |
dc.authorid | 0000-0002-9704-6173 | en_US |
dc.authorid | 0000-0003-1106-3288 | en_US |
dc.authorid | 0000-0001-6494-8923 | en_US |
dc.identifier.volume | 12 | en_US |
dc.identifier.startpage | 657 | en_US |
dc.identifier.endpage | 665 | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |
dc.identifier.doi | 10.1016/j.redox.2017.04.006 | en_US |
dc.identifier.wosquality | Q1 | en_US |
dc.identifier.scopusquality | Q1 | en_US |