title: C/EBPα and C/EBPβ binding proteins modulate hepatocyte apoptosis through iNOS signaling pathway.
abstract: 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.
authors.affiliation: Departments of Pediatrics and Surgery/Section of Pediatric Surgery, Rush University Medical Center, Chicago, IL 60612, USA. kewei_wang@rush.edu
authors.forename: Kewei
authors.initials: K
authors.lastname: Wang
authors.forename: John J
authors.initials: JJ
authors.lastname: Brems
authors.forename: Richard L
authors.initials: RL
authors.lastname: Gamelli
authors.forename: Ai-Xuan
authors.initials: AX
authors.lastname: Holterman
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005999:Glycochenodeoxycholic Acid / Q000494:pharmacology; D022781:Hepatocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D002352:Carrier Proteins; D017931:DNA Primers; D016328:NF-kappa B; D034741:RNA, Small Interfering; D005999:Glycochenodeoxycholic Acid; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat