Transcriptional effects of E3 ligase atrogin-1/MAFbx on apoptosis, hypertrophy and inflammation in neonatal rat cardiomyocytes.
Transcriptional effects of E3 ligase atrogin-1/MAFbx on apoptosis, hypertrophy and inflammation in neonatal rat cardiomyocytes.
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E3 连接酶 atrogin-1/MAFbx 对新生大鼠心肌细胞凋亡、肥大和炎症的转录作用。
DOI：
10.1371/journal.pone.0053831
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Li HH
中科院分区：
文献类型：
--
作者：
Zeng Y;Li J;Wang HX;Guo SB;Yang H;Zeng XJ;Fang Q;Tang CS;Du J;Li HH
Atrogin-1/MAFbx是一种泛素E3连接酶，通过泛素依赖性蛋白修饰调节心肌结构和功能。然而，关于atrogin-1激活对心肌细胞基因表达变化的影响知之甚少。用腺病毒atrogin-1（Ad-atrogin-1）或GFP对照（Ad-GFP）感染新生大鼠心肌细胞24小时。基因表达谱与微阵列分析进行比较。通过atrogin-1的过度表达，鉴定出314个差异表达基因，其中222个上调，92个下调。Atrogin-1过表达显著调节了30个主要功能类别的基因表达，大多数基因聚集在细胞死亡、增殖、炎症、代谢和心肌结构与功能的调节周围。此外，atrogin-1的过度表达显着抑制心肌细胞的存活，肥大和炎症基础条件下或响应脂多糖（LPS）。相反，通过siRNA敲低atrogin-1具有相反的效果。其作用机制与抑制MAPK（ERK 1/2、JNK 1/2和p38）和NF-κB信号通路有关。总之，目前的微阵列分析揭示了以前未被重视的atrogin-1调节基因，可能有助于atrogin-1对心肌细胞存活，肥大和炎症反应的影响内毒素，并可能提供新的见解如何atrogin-1调节心肌基因表达的编程。
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.
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影响因子：
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作者：
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影响因子：
18.2
作者：
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DOI：
10.1073/pnas.94.7.2897
发表时间：
1997-04-01
影响因子：
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作者：
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通讯作者：
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