Transcriptional Regulation of the Group IIA Secretory Phospholipase A2 Gene by C/EBPÃÂ´ in Rat liver and its Relationship to Hepatic luconeogenesis during Sepsis
- *Corresponding Author:
- Maw-Shung Liu
Graduate Institute of Medicine
Kaohsiung Medical University
Kaohsiung 802, Taiwan
Tel: 886-7-312-1101 ext 2136
Received Date: April 25, 2013; Accepted Date: August 26, 2013; Published Date: August 28, 2013
Citation: Yang RC, Hsu C, Lee TY, Kuo KK, Wu SM, et al. (2013) Transcriptional Regulation of the Group IIA Secretory Phospholipase A2 Gene by C/EBPd in Rat liver and its Relationship to Hepatic Gluconeogenesis during Sepsis. Emergency Med 3:151. doi:10.4172/2165-7548.1000151
Copyright: © 2013 Yang RC, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The present study was undertaken to test hypothesis that altered transcription of secretory Phospholipase A2 (sPLA2) gene in rat liver is regulated by CCAAT/enhancer binding protein δ (C/EBPδ), and to assess its relationship to hepatic gluconeogenesis during the progression of sepsis.
Sepsis was induced by Cecal Ligation and Puncture (CLP). Experiments were divided into three groups, control, early sepsis (9 h after CLP), and late sepsis (18 h after CLP).
DNA mobility and super shift assays reveal that C/EBP complexes in the liver consisted of at least three isoforms: C/EBPα, C/EBPβ, and C/EBPδ; and various C/EBP isoforms were capable of interacting with each other. Hepatocyte transfection experiments demonstrate that under normal conditions, binding of C/EBPδ to sPLA2 gene enhanced sPLA2 promoter activity and the binding resulted in an increase in hepatic gluconeogenesis. Under pathological conditions such as sepsis, binding of C/EBPδ to sPLA2 promoter increased during early and late phases of sepsis, and the increases in C/EBPδ binding correlated with increases in sPLA2 mRNA abundance and sPLA2 protein levels. Under otherwise the identical experimental conditions, hepatic gluconeogenesis was reduced during early and late phases of sepsis and the sepsis-induced reductions in liver gluconeogenesis were aggravated by binding of C/EBPδ to sPLA2 gene.
These results link C/EBPδ binding to altered sPLA2 promoter, and to hepatic gluconeogenesis under normal and pathological conditions. It is suggested that C/EBPδ-sPLA2- hepatic gluconeogenesis may function as a signalling axis affecting glucose homeostasis during the progression of sepsis.