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

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• 作者：Zelal Adiguzel (1)
  Nazli Arda (2)
  Omer Kacar (1)
  Muge Serhatli (1)
  Serpil Gezer Tas (3)
  Ahmet Tarik Baykal (4)
  Kemal Baysal (5)
  Ceyda Acilan (1)
  
  1. TUBITAK ; Marmara Research Center ; Genetic Engineering and Biotechnology Institute ; 41470 ; Gebze ; Kocaeli ; Turkey
  2. Department of Molecular Biology and Genetics ; Istanbul University ; 34134 ; Vezneciler ; Istanbul ; Turkey
  3. T.C. Ministry of Health ; Kartal Ko艧uyolu Advanced Training and Research Hospital ; 38846 ; Kartal ; Istanbul ; Turkey
  4. Department of Biochemistry ; Medical School ; Medipol University ; 34810 ; Kavac谋k ; Istanbul ; Turkey
  5. Health Services Vocational School ; Dokuz Eylul University ; 35340 ; Balcova ; Izmir ; Turkey
  
• 关键词：Thoracic aortic aneurysm ; Oxysterols ; Oxidative stress ; Reactive oxygen species ; Apoptosis
• 刊名：Molecular Biology Reports
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：41
• 期：12
• 页码：7875-7884
• 全文大小：1,411 KB
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• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Animal Anatomy, Morphology and Histology
  Animal Biochemistry
  
• 出版者：Springer Netherlands
• ISSN：1573-4978

文摘

Oxysterols, 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.