Integration of microarray profiles associated with cardiomyopathy and the potential role of Ube3a in apoptosis

Zhang,Jie; Song,Rui; Li,Yanfei; Feng,Jian; Peng,Luying; Li,Jue

doi:10.3892/mmr.2013.1848

Integration of microarray profiles associated with cardiomyopathy and the potential role of Ube3a in apoptosis

Authors:
- Jie Zhang
- Rui Song
- Yanfei Li
- Jian Feng
- Luying Peng
- Jue Li
View Affiliations

Affiliations: Division of Preventive Medicine, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, P.R. China, Key Laboratory of Arrhythmias, Ministry of Education, Tongji University School of Medicine, Shanghai 200092, P.R. China
Published online on: December 9, 2013 https://doi.org/10.3892/mmr.2013.1848
Pages: 621-625

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cardiomyopathy is the one of the primary causes of mortality. High‑throughput genome datasets provide novel information that aids the understanding of the complex mechanisms involved in cardiomyopathy. However, the causative mechanisms underlying cardiomyopathy are yet to be elucidated. In order to improve the use of the high‑throughput genome datasets, the present study employed 9 microarray datasets to mine for differentially expressed cardiomyopathy‑associated genes using bioinformatic methods. Following validation using quantitative polymerase chain reaction, ubiquitin‑protein ligase E3a (Ube3a) was selected as a candidate gene for the disease. Substantial evidence suggests that apoptosis may be involved in the pathophysiology of cardiomyopathies. Therefore, in the present study, H2O2 was utilized to induce apoptosis in H9C2 cells in order to understand the interrelation between Ube3a and the apoptosis-related protein p53. Ube3a and p53 were observed to be significantly increased at the transcriptional and translational levels in response to H2O2 treatment. The results of this study indicate the efficiency of the data integration and the significant interrelation between Ube3a and p53 in myocardial cells during apoptosis.

View Figures

View References

1	Sarkar S, Leaman DW, Gupta S, et al: Cardiac overexpression of myotrophin triggers myocardial hypertrophy and heart failure in transgenic mice. J Biol Chem. 279:20422–20434. 2004. View Article : Google Scholar : PubMed/NCBI
2	Schaub MC, Hefti MA and Zaugg M: Integration of calcium with the signaling network in cardiac myocytes. J Mol Cell Cardiol. 41:183–214. 2006. View Article : Google Scholar : PubMed/NCBI
3	Sarkar S, Chawla-Sarkar M, Young D, et al: Myocardial cell death and regeneration during progression of cardiac hypertrophy to heart failure. J Biol Chem. 279:52630–52642. 2004. View Article : Google Scholar : PubMed/NCBI
4	Shi PP, Cao XR, Sweezer EM, et al: Salt-sensitive hypertension and cardiac hypertrophy in mice deficient in the ubiquitin ligase Nedd4-2. Am J Physiol Renal Physiol. 295:F462–F470. 2008. View Article : Google Scholar : PubMed/NCBI
5	Haupt S, Berger M, Goldberg Z and Haupt Y: Apoptosis - the p53 network. J Cell Sci. 116:4077–4085. 2003. View Article : Google Scholar : PubMed/NCBI
6	Li HH, Willis MS, Lockyer P, et al: Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of Forkhead proteins. J Clin Invest. 117:3211–3223. 2007. View Article : Google Scholar : PubMed/NCBI
7	Weekes J, Morrison K, Mullen A, Wait R, Barton P and Dunn MJ: Hyperubiquitination of proteins in dilated cardiomyopathy. Proteomics. 3:208–216. 2003. View Article : Google Scholar : PubMed/NCBI
8	Matsuura T, Sutcliffe JS, Fang P, et al: De novo truncating mutations in E6-AP ubiquitin-protein ligase gene (UBE3A) in Angelman syndrome. Nat Genet. 15:74–77. 1997. View Article : Google Scholar : PubMed/NCBI
9	Huang HS, Allen JA, Mabb AM, et al: Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature. 481:185–189. 2011. View Article : Google Scholar : PubMed/NCBI
10	Bürger J, Horn D, Tönnies H, Neitzel H and Reis A: Familial interstitial 570 kbp deletion of the UBE3A gene region causing Angelman syndrome but not Prader-Willi syndrome. Am J Med Genet. 111:233–237. 2002.PubMed/NCBI
11	Veenstra-VanderWeele J, Gonen D, Leventhal BL and Cook EH Jr: Mutation screening of the UBE3A/E6-AP gene in autistic disorder. Mol Psychiatry. 4:64–67. 1999. View Article : Google Scholar : PubMed/NCBI
12	Maheshwari M, Samanta A, Godavarthi SK, Mukherjee R and Jana NR: Dysfunction of the ubiquitin ligase Ube3a may be associated with synaptic pathophysiology in a mouse model of Huntington disease. J Biol Chem. 287:29949–29957. 2012. View Article : Google Scholar : PubMed/NCBI
13	Long X, Boluyt MO, Hipolito ML, et al: p53 and the hypoxia-induced apoptosis of cultured neonatal rat cardiac myocytes. J Clin Invest. 99:2635–2643. 1997. View Article : Google Scholar : PubMed/NCBI
14	Shi L, Nikolic D, Liu S, Lu H and Wang S: Activation of renal renin-angiotensin system in upstream stimulatory factor 2 transgenic mice. Am J Physiol Renal Physiol. 296:F257–F265. 2009. View Article : Google Scholar : PubMed/NCBI
15	Blaxall BC, Spang R, Rockman HA and Koch WJ: Differential myocardial gene expression in the development and rescue of murine heart failure. Physiol Genomics. 15:105–114. 2003.PubMed/NCBI
16	Rysä J, Leskinen H, Ilves M and Ruskoaho H: Distinct upregulation of extracellular matrix genes in transition from hypertrophy to hypertensive heart failure. Hypertension. 45:927–933. 2005.PubMed/NCBI
17	da Silva R, Lucchinetti E, Pasch T, Schaub MC and Zaugg M: Ischemic but not pharmacological preconditioning elicits a gene expression profile similar to unprotected myocardium. Physiol Genomics. 20:117–130. 2004.
18	Fliegner D, Schubert C, Penkalla A, et al: Female sex and estrogen receptor-beta attenuate cardiac remodeling and apoptosis in pressure overload. Am J Physiol Regul Integr Comp Physiol. 298:R1597–R1606. 2010. View Article : Google Scholar : PubMed/NCBI
19	Kararigas G, Fliegner D, Gustafsson JÅ and Regitz-Zagrosek V: Role of the estrogen/estrogen-receptor-beta axis in the genomic response to pressure overload-induced hypertrophy. Physiol Genomics. 43:438–446. 2011. View Article : Google Scholar : PubMed/NCBI
20	Barth AS, Kuner R, Buness A, et al: Identification of a common gene expression signature in dilated cardiomyopathy across independent microarray studies. J Am Coll Cardiol. 48:1610–1617. 2006. View Article : Google Scholar : PubMed/NCBI
21	Husberg C, Nygård S, Finsen AV, et al: Cytokine expression profiling of the myocardium reveals a role for CX3CL1 (fractalkine) in heart failure. J Mol Cell Cardiol. 45:261–269. 2008. View Article : Google Scholar : PubMed/NCBI
22	Kittleson MM, Minhas KM, Irizarry RA, et al: Gene expression analysis of ischemic and nonischemic cardiomyopathy: shared and distinct genes in the development of heart failure. Physiol Genomics. 21:299–307. 2005. View Article : Google Scholar : PubMed/NCBI
23	Andersson KB, Florholmen G, Winer LH, Tønnessen T and Christensen G: Regulation of neuronal type genes in congestive heart failure rats. Acta Physiol (Oxf). 186:17–27. 2006. View Article : Google Scholar : PubMed/NCBI
24	Rhodes DR, Kalyana-Sundaram S, Mahavisno V, et al: Oncomine 3.0: genes, pathways, and networks in a collection of 18,000 cancer gene expression profiles. Neoplasia. 9:166–180. 2007. View Article : Google Scholar : PubMed/NCBI
25	Troyanskaya O, Cantor M, Sherlock G, et al: Missing value estimation methods for DNA microarrays. Bioinformatics. 17:520–525. 2001. View Article : Google Scholar : PubMed/NCBI
26	Irizarry RA, Warren D, Spencer F, et al: Multiple-laboratory comparison of microarray platforms. Nat Methods. 2:345–350. 2005. View Article : Google Scholar : PubMed/NCBI
27	Tusher VG, Tibshirani R and Chu G: Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA. 98:5116–5121. 2001. View Article : Google Scholar : PubMed/NCBI
28	Klipper-Aurbach Y, Wasserman M, Braunspiegel-Weintrob N, et al: Mathematical formulae for the prediction of the residual beta cell function during the first two years of disease in children and adolescents with insulin-dependent diabetes mellitus. Med Hypotheses. 45:486–490. 1995.PubMed/NCBI
29	Xie Y, Pan W and Khodursky AB: A note on using permutation-based false discovery rate estimates to compare different analysis methods for microarray data. Bioinformatics. 21:4280–4288. 2005. View Article : Google Scholar : PubMed/NCBI
30	Zhang S: A comprehensive evaluation of SAM, the SAM R-package and a simple modification to improve its performance. BMC Bioinformatics. 8:2302007. View Article : Google Scholar : PubMed/NCBI
31	Pavlidis P, Li Q and Noble WS: The effect of replication on gene expression microarray experiments. Bioinformatics. 19:1620–1627. 2003. View Article : Google Scholar : PubMed/NCBI
32	Clerk A, Kemp TJ, Zoumpoulidou G and Sugden PH: Cardiac myocyte gene expression profiling during H₂O₂-induced apoptosis. Physiol Genomics. 29:118–127. 2007. View Article : Google Scholar : PubMed/NCBI