title: Ionizing radiation induces immediate protein acetylation changes in human cardiac microvascular endothelial cells.
abstract: Reversible lysine acetylation is a highly regulated post-translational protein modification that is known to regulate several signaling pathways. However, little is known about the radiation-induced changes in the acetylome. In this study, we analyzed the acute post-translational acetylation changes in primary human cardiac microvascular endothelial cells 4 h after a gamma radiation dose of 2 Gy. The acetylated peptides were enriched using anti-acetyl conjugated agarose beads. A total of 54 proteins were found to be altered in their acetylation status, 23 of which were deacetylated and 31 acetylated. Pathway analyses showed three protein categories particularly affected by radiation-induced changes in the acetylation status: the proteins involved in the translation process, the proteins of stress response, and mitochondrial proteins. The activation of the canonical and non-canonical Wnt signaling pathways affecting actin cytoskeleton signaling and cell cycle progression was predicted. The protein expression levels of two nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases, sirtuin 1 and sirtuin 3, were significantly but transiently upregulated 4 but not 24 h after irradiation. The status of the p53 protein, a target of sirtuin 1, was found to be rapidly stabilized by acetylation after radiation exposure. These findings indicate that post-translational modification of proteins by acetylation and deacetylation is essentially affecting the radiation response of the endothelium.
authors.affiliation: Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany.
authors.forename: Zarko
authors.initials: Z
authors.lastname: Barjaktarovic
authors.affiliation: Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Kempf
authors.affiliation: Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany.
authors.forename: Arundhathi
authors.initials: A
authors.lastname: Sriharshan
authors.affiliation: Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany.
authors.forename: Juliane
authors.initials: J
authors.lastname: Merl-Pham
authors.affiliation: Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Atkinson
authors.affiliation: Helmholtz Zentrum München, Ingolstädter Landstraße 1, Neuherberg 85764, Germany soile.tapio@helmholtz-muenchen.de.
authors.forename: Soile
authors.initials: S
authors.lastname: Tapio
mesh_terms: D000107:Acetylation / Q000528:radiation effects*; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D042783:Endothelial Cells / Q000502:physiology* / Q000528:radiation effects*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008239:Lysine / Q000378:metabolism*; D055806:Microvessels / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D009206:Myocardium / Q000166:cytology; D020543:Proteome / Q000378:metabolism*; D011829:Radiation Dosage; D011839:Radiation, Ionizing
chemical_list: D020543:Proteome; D006655:Histone Deacetylases; D008239:Lysine
keywords: acetylation; endothelial cell; heart; ionizing radiation; proteomics; sirtuins
references.citation: Cell Signal. 2010 Apr;22(4):668-75
references.pmid: 20004716
references.citation: Biochem J. 2011 Jan 1;433(1):205-13
references.pmid: 20942800
references.citation: Oncogene. 2011 Sep 15;30(37):3979-84
references.pmid: 21532622
references.citation: Radiat Environ Biophys. 2011 Mar;50(1):155-66
references.pmid: 21104263
references.citation: Nature. 1970 Aug 15;227(5259):680-5
references.pmid: 5432063
references.citation: RNA. 2009 Jan;15(1):153-75
references.pmid: 19029308
references.citation: Cell Death Differ. 2006 Jun;13(6):1027-36
references.pmid: 16557269
references.citation: Cell. 2008 Nov 28;135(5):797-8
references.pmid: 19041745
references.citation: J Proteomics. 2012 Apr 18;75(8):2319-30
references.pmid: 22370162
references.citation: J Cell Biol. 1999 Dec 27;147(7):1431-42
references.pmid: 10613902
references.citation: Annu Rev Biochem. 2007;76:75-100
references.pmid: 17362198
references.citation: J Biomed Biotechnol. 2011;2011:970382
references.pmid: 21151618
references.citation: Nat Rev Mol Cell Biol. 2005 Apr;6(4):318-27
references.pmid: 15803138
references.citation: Mol Cell. 2009 Dec 25;36(6):932-41
references.pmid: 20064460
references.citation: J Biol Chem. 2010 Apr 30;285(18):13507-16
references.pmid: 20181957
references.citation: Proteomics. 2011 Aug;11(16):3299-311
references.pmid: 21751382
references.citation: Genes Cancer. 2013 Mar;4(3-4):112-7
references.pmid: 24020002
references.citation: J Proteome Res. 2010 Sep 3;9(9):4710-20
references.pmid: 20604508
references.citation: Cell. 2001 Oct 19;107(2):137-48
references.pmid: 11672522
references.citation: Radiat Environ Biophys. 2013 Mar;52(1):87-98
references.pmid: 23138885
references.citation: Biochim Biophys Acta. 2010 Jul;1803(7):865-71
references.pmid: 20362631
references.citation: Genes Dev. 2009 Feb 1;23(3):265-77
references.pmid: 19204114
references.citation: Wiley Interdiscip Rev RNA. 2010 Nov-Dec;1(3):486-93
references.pmid: 21956944
references.citation: Mech Dev. 2007 Sep-Oct;124(9-10):682-98
references.pmid: 17716875
references.citation: J Biol Chem. 2010 Apr 9;285(15):11458-64
references.pmid: 20100829
references.citation: Cell. 1997 Feb 7;88(3):323-31
references.pmid: 9039259
references.citation: Dev Dyn. 2008 Aug;237(8):2158-69
references.pmid: 18651656
references.citation: Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):656-65
references.pmid: 20159360
references.citation: Mol Interv. 2004 Dec;4(6):348-57
references.pmid: 15616164
references.citation: Nature. 2009 May 7;459(7243):113-7
references.pmid: 19270680
references.citation: Oncogene. 2007 Aug 13;26(37):5505-20
references.pmid: 17694090
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 15;99(21):13653-8
references.pmid: 12374852
references.citation: Nat Rev Mol Cell Biol. 2007 Apr;8(4):284-95
references.pmid: 17380162
references.citation: Cell. 2001 Oct 19;107(2):149-59
references.pmid: 11672523
references.citation: Nat Cell Biol. 2003 Apr;5(4):320-9
references.pmid: 12652308
references.citation: Mol Cell Proteomics. 2010 Oct;9(10):2292-305
references.pmid: 20601722
references.citation: Trends Endocrinol Metab. 2012 Sep;23(9):467-76
references.pmid: 22902903
references.citation: Mol Cell Biol. 2007 Dec;27(24):8502-9
references.pmid: 17923702
references.citation: Biochem Biophys Res Commun. 2000 Jul 5;273(2):793-8
references.pmid: 10873683
references.citation: Mol Biol Cell. 2009 Jan;20(1):419-27
references.pmid: 18987336
references.citation: Proc Natl Acad Sci U S A. 2010 May 18;107(20):9216-21
references.pmid: 20439735
references.citation: Radiat Oncol. 2013;8:35
references.pmid: 23402580
references.citation: Mol Cell. 2006 Aug;23(4):607-18
references.pmid: 16916647
references.citation: Trends Cell Biol. 2010 Jul;20(7):427-34
references.pmid: 20399660
references.citation: Genes Dev. 1998 Sep 15;12(18):2831-41
references.pmid: 9744860
references.citation: Science. 2004 Dec 17;306(5704):2105-8
references.pmid: 15604409
references.citation: Mol Cell Biol. 2008 Oct;28(20):6384-401
references.pmid: 18710944
references.citation: Mol Cell Biol. 2009 Nov;29(21):5645-56
references.pmid: 19704005
references.citation: Crit Rev Oncol Hematol. 2003 Jan;45(1):55-75
references.pmid: 12482572
references.citation: Gastroenterology. 2005 Jun;128(7):1907-18
references.pmid: 15940626
references.citation: Science. 2009 Aug 14;325(5942):834-40
references.pmid: 19608861
references.citation: Mol Cell. 2004 Oct 8;16(1):93-105
references.pmid: 15469825
references.citation: Proteomes. 2014 Jun;2(2):272-290
references.pmid: 26269784
references.citation: Cell Physiol Biochem. 2007;20(1-4):45-54
references.pmid: 17595514
references.citation: BMJ. 2003 Feb 1;326(7383):256-7
references.pmid: 12560277
references.citation: FEBS Lett. 2012 Sep 21;586(19):3236-41
references.pmid: 22771473
references.citation: Mol Cell Biol. 2012 Jul;32(14):2823-36
references.pmid: 22586264
references.citation: Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15853-8
references.pmid: 23019370
references.citation: Mol Cell. 2012 Apr 27;46(2):212-25
references.pmid: 22424773
references.citation: Free Radic Biol Med. 2013 Mar;56:133-71
references.pmid: 23104101
references.citation: J Proteomics. 2012 Apr 18;75(8):2384-95
references.pmid: 22387116
references.citation: Cell. 2012 Jun 8;149(6):1192-205
references.pmid: 22682243
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 23;105(38):14447-52
references.pmid: 18794531
references.citation: Cell. 1997 Aug 22;90(4):595-606
references.pmid: 9288740
references.citation: Mol Cell Biol. 2006 Jan;26(1):28-38
references.pmid: 16354677
references.citation: Cardiovasc Res. 2014 Mar 1;101(3):444-53
references.pmid: 24293519
references.citation: Biochem J. 1995 Nov 15;312 ( Pt 1):163-7
references.pmid: 7492307
references.citation: Genes Cancer. 2011 Jun;2(6):648-62
references.pmid: 21941620
references.citation: N Engl J Med. 2013 Mar 14;368(11):987-98
references.pmid: 23484825