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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Chronic exposure to low-dose ionizing radiation is associated with an increased risk of cardiovascular disease. Alteration in energy metabolism has been suggested to contribute to radiation-induced heart pathology, mitochondrial dysfunction being a hallmark of this disease. The goal of this study was to investigate the regulatory role of acetylation in heart mitochondria in the long-term response to chronic radiation. ApoE-deficient C57Bl/6J mice were exposed to low-dose-rate (20 mGy/day) gamma radiation for 300 days, resulting in a cumulative total body dose of 6.0 Gy. Heart mitochondria were isolated and analyzed using quantitative proteomics. Radiation-induced proteome and acetylome alterations were further validated using immunoblotting, enzyme activity assays, and ELISA. In total, 71 proteins showed peptides with a changed acetylation status following irradiation. The great majority (94%) of the hyperacetylated proteins were involved in the TCA cycle, fatty acid oxidation, oxidative stress response and sirtuin pathway. The elevated acetylation patterns coincided with reduced activity of mitochondrial sirtuins, increased the level of Acetyl-CoA, and were accompanied by inactivation of major cardiac metabolic regulators PGC-1 alpha and PPAR alpha. These observations suggest that the changes in mitochondrial acetylation after irradiation is associated with impairment of heart metabolism. We propose a novel mechanism involved in the development of late cardiac damage following chronic irradiation.

Details

Title
Hyperacetylation of Cardiac Mitochondrial Proteins Is Associated with Metabolic Impairment and Sirtuin Downregulation after Chronic Total Body Irradiation of ApoE -/- Mice
Author
Barjaktarovic, Zarko 1 ; Merl-Pham, Juliane 2 ; Braga-Tanaka, Ignacia 3 ; Tanaka, Satoshi 3 ; Hauck, Stefanie M 2 ; Saran, Anna 4 ; Mancuso, Mariateresa 4 ; Atkinson, Michael J 5 ; Soile Tapio 6 ; Azimzadeh, Omid 6 

 Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Institute of Radiation Biology, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; [email protected] (Z.B.); [email protected] (M.J.A.); [email protected] (S.T.); Agency for Medicines and Medical Devices of Montenegro, 81000 Podgorica, Montenegro 
 Research Unit Protein Science, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 80939 München, Germany; [email protected] (J.M.-P.); [email protected] (S.M.H.) 
 Institute for Environmental Sciences (IES), Rokkasho, Aomori 039-3213, Japan; [email protected] (I.B.-T.); [email protected] (S.T.) 
 Laboratory of Biomedical Technologies, Agenzia Nazionale per le Nuove Tecnologie, l’Energia e lo Sviluppo Economico Sostenibile (ENEA), 76 00196 Rome, Italy; [email protected] (A.S.); [email protected] (M.M.) 
 Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Institute of Radiation Biology, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; [email protected] (Z.B.); [email protected] (M.J.A.); [email protected] (S.T.); Chair of Radiation Biology, Technical University Munich, 80333 Munich, Germany 
 Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, Institute of Radiation Biology, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany; [email protected] (Z.B.); [email protected] (M.J.A.); [email protected] (S.T.) 
First page
5239
Publication year
2019
Publication date
2019
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2548679230
Copyright
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.