C/EBPα and C/EBPβ binding proteins modulate hepatocyte apoptosis through iNOS signaling pathway

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• 作者：Kewei Wang^a ; ^{kewei_wang@rush.edu"" rel=""nofollow} ; John J. Brems^b ; Richard L. Gamelli^b ; Ai-Xuan Holterman^a
• 关键词：Apoptosis ; Hepatocyte ; iNOS ; C/EBPα ; C/EBPβ ; Signal transduction
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular Cell Research
• 出版年：2011
• 出版时间：August 2011
• 年：2011
• 卷：1813
• 期：8
• 页码：1395-1403
• 全文大小：758 K

文摘

Inducible nitric oxide synthase (iNOS) and nitric oxide (NO) involve many pathophysiologic conditions. The expression of iNOS is regulated at multiple stages. Presently, the regulatory details of iNOS signaling are still unclear. This study aimed to investigate the regulatory role of C/EBPα and C/EBPβ in iNOS signaling pathway. By employing the techniques such as EMSA, ChIP assay, site-directed mutagenesis, and siRNA silencing, the relationship between iNOS and C/EBPα/C/EBPβ in rat hepatocytes was clarified. iNOS promoter was the direct transcriptional targets of the C/EBPα, C/EBPβ, and NF-κB binding proteins. There was the interactive influence between NF-κB and C/EBPα/C/EBPβ. The expression of iNOS was modulated by C/EBPα/C/EBPβ transcription factors. Moreover, the iNOS expression mediated glycochenodeoxycholate (GCDC)-induced apoptosis in hepatocytes. C/EBPα/C/EBPβ binding proteins could affect the GCDC-induced apoptosis through iNOS cascade. These findings indicate that C/EBPα and C/EBPβ regulate the iNOS expression, which may further modify cell responses such as apoptosis and cell survival.