title: Prothymosin alpha protects cardiomyocytes against ischemia-induced apoptosis via preservation of Akt activation.
abstract: 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.
authors.affiliation: Division of Cardiology, Department of Advanced Biomedical Sciences, Federico II University of Naples, Via Pansini, 5, 80131, Naples, Italy, cannavo.alessandro@gmail.com.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Cannavo
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rengo
authors.forename: Daniela
authors.initials: D
authors.lastname: Liccardo
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Pironti
authors.forename: Maria Cecilia
authors.initials: MC
authors.lastname: Scimia
authors.forename: Laura
authors.initials: L
authors.lastname: Scudiero
authors.forename: Claudio
authors.initials: C
authors.lastname: De Lucia
authors.forename: Marco
authors.initials: M
authors.lastname: Ferrone
authors.forename: Dario
authors.initials: D
authors.lastname: Leosco
authors.forename: Nicola
authors.initials: N
authors.lastname: Zambrano
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Koch
authors.forename: Bruno
authors.initials: B
authors.lastname: Trimarco
authors.forename: Giovanni
authors.initials: G
authors.lastname: Esposito
mesh_terms: D000818:Animals; D017209:Apoptosis; D015687:Cell Hypoxia; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism* / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013947:Thymosin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D011498:Protein Precursors; C040782:prothymosin alpha; D013947:Thymosin; D051057:Proto-Oncogene Proteins c-akt