Evaluation of apoptotic molecular pathways for smooth muscle cells isolated from thoracic aortic aneurysms in response to oxidized sterols

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dc.authorid0000-0002-8814-7351
dc.contributor.authorAdıgüzel, Zelal
dc.contributor.authorArda, Nazlı
dc.contributor.authorKaçar, Ömer
dc.contributor.authorSerhatlı, Müge
dc.contributor.authorGezer Taş, Serpil
dc.contributor.authorBaykal, Ahmet Tarık
dc.contributor.authorBaysal, Kemal
dc.contributor.authorAçılan, Ceyda
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T20:01:49Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T20:01:49Z
dc.date.issued2014
dc.departmentİstanbul Medipol Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyokimya Ana Bilim Dalı
dc.descriptionWOS: 000349005800018
dc.descriptionPubMed ID: 25266234
dc.description.abstractOxysterols, oxygenated derivatives of cholesterol, are found abundantly in the plasma and atherosclerotic plaques, a common risk factor for thoracic aortic aneurysms (TAAs). Among the oxysterols, namely 7-ketocholesterol (7-KC) and 25-hydroxycholesterol (25-OHC), lead both to induction of reactive oxygen species (ROS) in cells and to apoptosis in smooth muscle cells (SMCs) probably due to increased oxidative stress. Since loss of SMCs through apoptosis is a major event in TAA formation, it is important to understand the molecular pathways of apoptosis in response to ROS in TAAs. Very little is known about the effect of oxysterols on TAA SMCs. Therefore, we investigated molecular pathways participating in the oxysterol induced cell death of TAAs. Our results showed that TAA SMCs died mainly as a result of apoptosis as suggested by cellular shrinkage, blebbing, DNA condensation/fragmentation in response to oxysterol treatment. There was no significant difference in oxysterol induced cell death between TAA and control SMCs. Addition of antioxidant molecules prevented cell death, hence ROS appears to be involved in the apoptosis of these cells. While oxysterol treatment increased caspase 3 activity, cell death was not rescued in its absence. Efficient silencing of other targets including apoptotic proteins (p53, Bax), and survival proteins (Akt1, Akt2) showed that apoptosis can occur through p53, and Bax independent pathways. Silencing Akt1 or Akt2 did not lead to further cell death. These results indicate that oxysterols can induce several cell death pathways in TAA SMCs.
dc.description.sponsorshipFP7 Project entitled "Fighting Aneurysmal Disease" (FAD) [200647]en_US
dc.description.sponsorshipIstanbul University Department of Scientific Research Projects [10241]en_US
dc.description.sponsorshipThis work was supported by the FP7 Project entitled "Fighting Aneurysmal Disease" (FAD), Grant No: 200647 and Istanbul University Department of Scientific Research Projects, entitled "Investigation of Gene Expressions Related to Oxidative Stress in Human Thoracic Aort Aneurysms", Grant No: 10241.en_US
dc.identifier.citationAdıgüzel, Z., Arda, N., Kaçar, Ö., Serhatlı, M., Gezer Taş, S., Baykal, A. T., Baysal, K. ... Açılan, C. (2014). Evaluation of apoptotic molecular pathways for smooth muscle cells isolated from thoracic aortic aneurysms in response to oxidized sterols. Molecular Biology Reports, 41(12), 7875-7884. https://dx.doi.org/10.1007/s11033-014-3681-9
dc.identifier.doi10.1007/s11033-014-3681-9
dc.identifier.endpage7884
dc.identifier.issn0301-4851
dc.identifier.issn1573-4978
dc.identifier.issue12
dc.identifier.scopusqualityQ2
dc.identifier.startpage7875
dc.identifier.urihttps://dx.doi.org/10.1007/s11033-014-3681-9
dc.identifier.urihttps://hdl.handle.net/20.500.12511/3457
dc.identifier.volume41
dc.identifier.wosqualityQ4
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherSpringer
dc.relation.ispartofMolecular Biology Reportsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/embargoedAccess
dc.subjectThoracic Aortic Aneurysm
dc.subjectOxysterols
dc.subjectOxidative Stress
dc.subjectReactive Oxygen Species
dc.subjectApoptosis
dc.titleEvaluation of apoptotic molecular pathways for smooth muscle cells isolated from thoracic aortic aneurysms in response to oxidized sterols
dc.typeArticle

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