Proteomic analyses of age related changes in A.BY/SnJ mouse hearts

Proteome Science

Elke Hammer³  Karin Klingel¹  Uwe Völker³  Stephan B Felix²  Reinhard Kandolf¹  Manuela Gesell Salazar³  Martina Sauter¹  Leif Steil³  Truong Quoc Phong³  Krishnatej Nishtala³ 

[1] Abteilung Molekulare Pathologie, Universitätsklinikum Tübingen, Tübingen, Germany;Klinik für Innere Medizin B, Universitätsmedizin Greifswald, Greifswald, Germany;Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Universitätsmedizin Greifswald, Friedrich-Ludwig-Jahn-Str. 15A, 17487Greifswald, Germany

关键词: LC-MS based quantitation;    Differential in-gel electrophoresis;    Murine model;    Hearts;    Aging;   

Others  :  816859
DOI  :  10.1186/1477-5956-11-29

 received in 2013-01-04, accepted in 2013-06-11,  发布年份 2013

【 摘 要 】

Background

A.BY/SnJ mice are used to study pathological alterations in the heart due to enteroviral infections. Since age is a well-known factor influencing the susceptibility of mice to infection, response to stress and manifestation of cardiovascular diseases, the myocardial proteome of A.BY/SnJ mice aged 1 and 4 months was comparatively studied using two dimensional-differential in-gel electrophoresis (2D-DIGE) and liquid chromatography tandem mass spectrometry (LC-MS/MS).

Results

Complementary analyses by 2D-DIGE and gel-free LC-MS/MS revealed 96 distinct proteins displaying age associated alterations in their levels. Proteins related to protein transport, and transport chain, lipid metabolism and fatty acid transport showed significant changes in 4 months old mouse hearts compared to juvenile hearts. Proteins involved in lipid metabolism and transport were identified at significantly higher levels in older mice and dysregulation of proteins of the respiratory transport chain were observed.

Conclusion

The current proteomics study discloses age dependent changes occurring in the hearts already in young mice of the strain A.BY/SnJ. Besides alterations in protein transport, we provide evidence that a decrease of ATP synthase in murine hearts starts already in the first months of life, leading to well-known low expression levels manifested in old mice thereby raising the possibility of reduced energy supply. In the first few months of murine life this seems to be compensated by an increased lipid metabolism. The functional alterations described should be considered during experimental setups in disease related studies.

【 授权许可】

   
2013 Nishtala et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Lakatta EG: Age-associated cardiovascular changes in health: impact on cardiovascular disease in older persons. Heart Fail Rev 2002, 7:29-49.
• [2]Oxenham H, Sharpe N: Cardiovascular aging and heart failure. Eur J Heart Fail 2003, 5:427-434.
• [3]Shih H, Lee B, Lee RJ, Boyle AJ: The aging heart and post-infarction left ventricular remodeling. J Am Coll Cardiol 2011, 57:9-17.
• [4]Simkhovich BZ, Marjoram P, Poizat C, Kedes L, Kloner RA: Age-related changes of cardiac gene expression following myocardial ischemia/reperfusion. Arch Biochem Biophys 2003, 420:268-278.
• [5]Lakatta EG: Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part III: cellular and molecular clues to heart and arterial aging. Circulation 2003, 107:490-497.
• [6]Padrao AI, Ferreira R, Vitorino R, Alves RM, et al.: Effect of lifestyle on age-related mitochondrial protein oxidation in mice cardiac muscle. Eur J Appl Physiol 2012, 112:1467-1474.
• [7]Kanski J, Behring A, Pelling J, Schoneich C: Proteomic identification of 3-nitrotyrosine-containing rat cardiac proteins: effects of biological aging. Am J Physiol Heart Circ Physiol 2005, 288:H371-H381.
• [8]Kiri AN, Tran HC, Drahos KL, Lan W, et al.: Proteomic changes in bovine heart mitochondria with age: using a novel technique for organelle separation and enrichment. J Biomol Tech 2005, 16:371-379.
• [9]Klingel K, Hohenadl C, Canu A, Albrecht M, et al.: Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation. Proc Natl Acad Sci U S A 1992, 89:314-318.
• [10]Gay RT, Belisle S, Beck MA, Meydani SN: An aged host promotes the evolution of avirulent coxsackievirus into a virulent strain. Proc Natl Acad Sci U S A 2006, 103:13825-13830.
• [11]Nakamura H, Yamamura T, Fukuta S, Matsumori A, Matsuzaki M: A pathogenic mechanism of chronic ongoing myocarditis. Jpn Circ J 1996, 60:609-617.
• [12]Hammer E, Phong TQ, Steil L, Klingel K, et al.: Viral myocarditis induced by Coxsackievirus B3 in A.BY/SnJ mice: analysis of changes in the myocardial proteome. Proteomics 2010, 10:1802-1818.
• [13]Nishtala K, Phong TQ, Steil L, Sauter M, et al.: Virus-induced dilated cardiomyopathy is characterized by increased levels of fibrotic extracellular matrix proteins and reduced amounts of energy-producing enzymes. Proteomics 2011, 11:4310-4320.
• [14]Dai Q, Escobar GP, Hakala KW, Lambert JM, et al.: The left ventricle proteome differentiates middle-aged and old left ventricles in mice. J Proteome Res 2008, 7:756-765.
• [15]Chakravarti B, Oseguera M, Dalal N, Fathy P, et al.: Proteomic profiling of aging in the mouse heart: Altered expression of mitochondrial proteins. Arch Biochem Biophys 2008, 474:22-31.
• [16]Grant JE, Bradshaw AD, Schwacke JH, Baicu CF, et al.: Quantification of protein expression changes in the aging left ventricle of Rattus norvegicus. J Proteome Res 2009, 8:4252-4263.
• [17]Walther DM, Mann M: Accurate quantification of more than 4000 mouse tissue proteins reveals minimal proteome changes during aging. Mol Cell Proteomics 2011, 10:M110 004523.
• [18]Jungblut PR, Holzhutter HG, Apweiler R, Schluter H: The speciation of the proteome. Chem Central J 2008, 2:16. BioMed Central Full Text
• [19]Olivetti G, Melissari JM, Capasso J, Anversa P: Cardiomyopathy of the aging human heart. Myocyte loss and reactive cellular hypertrophy. Circulation Res 1991, 68:1560-1568.
• [20]Yoshida K, Nogami S, Satoh S, Tanaka-Nakadate S, et al.: Interaction of the taxilin family with the nascent polypeptide-associated complex that is involved in the transcriptional and translational processes. Genes Cells 2005, 10:465-476.
• [21]Nogami S, Satoh S, Tanaka-Nakadate S, Yoshida K, et al.: Identification and characterization of taxilin isoforms. Biochem Biophys Res Commun 2004, 319:936-943.
• [22]Fujimori KE, Uyeda A, Taguchi T: Regulatory expression of MDP77 protein in the skeletal and cardiac muscles. FEBS Lett 2002, 529:303-308.
• [23]Masumiya H, Asaumi Y, Nishi M, Minamisawa S, et al.: Mitsugumin 53-mediated maintenance of K + currents in cardiac myocytes. Channels (Austin) 2009, 3:6-11.
• [24]Cai C, Masumiya H, Weisleder N, Pan Z, et al.: MG53 regulates membrane budding and exocytosis in muscle cells. J Biol Chem 2009, 284:3314-3322.
• [25]Cai C, Masumiya H, Weisleder N, Matsuda N, et al.: MG53 nucleates assembly of cell membrane repair machinery. Nat Cell Biol 2009, 11:56-64.
• [26]Yang C, Slepnev VI, Goud B: Rab proteins form in vivo complexes with two isoforms of the GDP-dissociation inhibitor protein (GDI). J Biol Chem 1994, 269:31891-31899.
• [27]Pleasure IT, Black MM, Keen JH: Valosin-containing protein, VCP, is a ubiquitous clathrin-binding protein. Nature 1993, 365:459-462.
• [28]Chung SK, Kim JY, Kim IB, Park SI, et al.: Internalization and trafficking mechanisms of coxsackievirus B3 in HeLa cells. Virology 2005, 333:31-40.
• [29]Vembar SS: One step at a time: endoplasmic reticulum- associated degradation. Nat Rev 2008, 9:944-957.
• [30]Brandt JM, Djouadi F, Kelly DP: Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor alpha. J Biol Chem 1998, 273:23786-23792.
• [31]Paradies G, Ruggiero FM: Age-related changes in the activity of the pyruvate carrier and in the lipid composition in rat-heart mitochondria. Biochim Biophys Acta 1990, 1016:207-212.
• [32]Paradies G, Petrosillo G, Gadaleta MN, Ruggiero FM: The effect of aging and acetyl-L-carnitine on the pyruvate transport and oxidation in rat heart mitochondria. FEBS Lett 1999, 454:207-209.
• [33]Bodyak N, Kang PM, Hiromura M, Sulijoadikusumo I, et al.: Gene expression profiling of the aging mouse cardiac myocytes. Nucleic Acids Res 2002, 30:3788-3794.
• [34]Thiele T, Steil L, Gebhard S, Scharf C, et al.: Profiling of alterations in platelet proteins during storage of platelet concentrates. Transfusion 2007, 47:1221-1233.
• [35]Blum H, Beier H, Gross HJ: Improved silver staining of plant proteins, RNA and DNA in polyacrylamide gels. Electrophoresis 1987, 8:93-99.
• [36]Cima I, Schiess R, Wild P, Kaelin M, et al.: Cancer genetics-guided discovery of serum biomarker signatures for diagnosis and prognosis of prostate cancer. Proc Natl Acad Sci U S A 2011, 108:3342-3347.
• [37]Old WM, Meyer-Arendt K, Aveline-Wolf L, Pierce KG, et al.: Comparison of label-free methods for quantifying human proteins by shotgun proteomics. Mol Cell Proteomics 2005, 4:1487-1502.