1. Transcriptional Effects of E3 Ligase Atrogin-1/MAFbx on Apoptosis, Hypertrophy and Inflammation in Neonatal Rat Cardiomyocytes
- Author
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Yong Zeng, Junjie Li, Hong-Xia Wang, Shu-Bin Guo, Hui Yang, Xiang-Jun Zeng, Quan Fang, Chao-Shu Tang, Jie Du, and Hui-Hua Li
- Subjects
Gene Expression ,Muscle Proteins ,lcsh:Medicine ,Apoptosis ,Cardiomegaly ,Biology ,Cardiovascular ,Muscle hypertrophy ,Gene expression ,Animals ,Cluster Analysis ,Myocytes, Cardiac ,lcsh:Science ,Cell Proliferation ,Inflammation ,Regulation of gene expression ,Heart Failure ,Gene knockdown ,SKP Cullin F-Box Protein Ligases ,Multidisciplinary ,Microarray analysis techniques ,Gene Expression Profiling ,lcsh:R ,NF-kappa B ,Reproducibility of Results ,Rats ,Cell biology ,Ubiquitin ligase ,Gene expression profiling ,Gene Expression Regulation ,biology.protein ,Medicine ,lcsh:Q ,Mitogen-Activated Protein Kinases ,Signal transduction ,Cardiomyopathies ,Metabolic Networks and Pathways ,Signal Transduction ,Research Article - Abstract
Atrogin-1/MAFbx is an ubiquitin E3 ligase that regulates myocardial structure and function through the ubiquitin-dependent protein modification. However, little is known about the effect of atrogin-1 activation on the gene expression changes in cardiomyocytes. Neonatal rat cardiomyocytes were infected with adenovirus atrogin-1 (Ad-atrogin-1) or GFP control (Ad-GFP) for 24 hours. The gene expression profiles were compared with microarray analysis. 314 genes were identified as differentially expressed by overexpression of atrogin-1, of which 222 were up-regulated and 92 were down-regulated. Atrogin-1 overexpression significantly modulated the expression of genes in 30 main functional categories, most genes clustered around the regulation of cell death, proliferation, inflammation, metabolism and cardiomyoctye structure and function. Moreover, overexpression of atrogin-1 significantly inhibited cardiomyocyte survival, hypertrophy and inflammation under basal condition or in response to lipopolysaccharide (LPS). In contrast, knockdown of atrogin-1 by siRNA had opposite effects. The mechanisms underlying these effects were associated with inhibition of MAPK (ERK1/2, JNK1/2 and p38) and NF-κB signaling pathways. In conclusion, the present microarray analysis reveals previously unappreciated atrogin-1 regulation of genes that could contribute to the effects of atrogin-1 on cardiomyocyte survival, hypertrophy and inflammation in response to endotoxin, and may provide novel insight into how atrogin-1 modulates the programming of cardiac muscle gene expression.
- Published
- 2013