Prothymosin alpha protects cardiomyocytes against ischemia-induced apoptosis via preservation of Akt activation

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• 作者：Alessandro Cannavo ; Giuseppe Rengo ; Daniela Liccardo ; Gianluigi Pironti…
• 关键词：Prothymosin alpha ; Apoptosis ; Ischemia ; Cardioprotection
• 刊名：Apoptosis
• 出版年：2013
• 出版时间：October 2013
• 年：2013
• 卷：18
• 期：10
• 页码：1252-1261
• 全文大小：607KB
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• 作者单位：Alessandro Cannavo (1) (2) (3)
  Giuseppe Rengo (3) (4)
  Daniela Liccardo (3)
  Gianluigi Pironti (1) (5)
  Maria Cecilia Scimia (2)
  Laura Scudiero (1)
  Claudio De Lucia (3)
  Marco Ferrone (1)
  Dario Leosco (3)
  Nicola Zambrano (6) (7)
  Walter J. Koch (2)
  Bruno Trimarco (1)
  Giovanni Esposito (1)
  
  1. Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Via Pansini, 5, 80131, Naples, Italy
  2. Center for Translational Medicine, Temple University, Philadelphia, PA, USA
  3. Division of Geriatrics, Department of Translational Medical Sciences, Federico II University of Naples, Naples, Italy
  4. Division of Cardiology, Salvatore Maugeri Foundation, IRCCS, Scientific Institute of Telese Terme, Telese Terme, BN, Italy
  5. Duke University, Durham, NC, USA
  6. Department of Biochemistry and Medical Biotechnology, Federico II University of Naples, Naples, Italy
  7. CEINGE Advanced Biotechnology, Naples, Italy
  
• ISSN：1573-675X

文摘

The human prothymosin alpha (PTα) gene encodes a 12.5?kDa highly acidic nuclear protein that is widely expressed in mammalian tissues including the heart and importantly, is detectable also in blood serum. During apoptosis or necrosis, PTα changes its nuclear localization and is able to exert an important cytoprotective effect. Since the role of PTα in the heart has never been evaluated, the aim of the present study was to investigate the effects of PTα on cardiomyocytes during ischemic injury. Our data show that seven after myocardial infarction (MI), PTα expression levels are significantly increased both in blood serum and in cardiac tissue, and notably we observe that PTα translocates from the nuclei to cytoplasm and plasma membrane of cardiomyocytes following MI. Furthermore, in vitro experiments in cardiomyocytes, confirm that after 6?h of simulated ischemia (SI), PTα protein levels are upregulated compared to normoxic cells. Importantly, treatment of cardiomyocytes with a recombinant PTα (rPTα), during SI results in a significant decrease in the apoptotic response and in a robust increase in cell survival. Moreover, these effects are accompanied to a significant preservation of the activated levels of the anti-apoptotic serine-threonine kinase Akt. Consistent with our in vitro observation, rPTα-treated MI mice exhibit a strong reduction in infarct size at 24?h, compared to the MI control group and at the molecular level, PTα treatment induces activation of Akt. The present study provides for the first time the demonstration that PTα offers cardioprotection against ischemic injury by an Akt-dependent mechanism.