Serum after Partial Hepatectomy Stimulates iNOS Gene Transcription via Downstream NF-κB Site

It has been known that the expression of inducible nitric oxide synthase (iNOS) is up-regulated during hepatic regeneration. The present study characterized the molecular mechanisms involved in the transcriptional activation of iNOS gene by using the serum after partial hepatectomy (post-PH serum) i...

Full description

Saved in:
Bibliographic Details
Published in:Biochemical and biophysical research communications 2001-06, Vol.284 (3), p.607-613
Main Authors: Hur, Gang Min, Ryu, Young Sue, Hong, Jang Hee, Bae, So Hyun, Bae, Jin Young, Paik, Sang Gi, Kim, Yong Man, Seok, Jeong Ho, Lee, Jae Heun
Format: Article
Language:English
Subjects:
Animals
Antibodies - immunology
Blood
Cell Line
Culture Media
Hepatectomy
iNOS gene
Kinetics
Liver Regeneration
Mice
NF-kappa B - metabolism
Nitric Oxide Synthase - biosynthesis
Nitric Oxide Synthase - genetics
Nitric Oxide Synthase Type II
Promoter Regions, Genetic
Rats
Rats, Sprague-Dawley
Response Elements
RNA, Messenger - biosynthesis
Transcriptional Activation
Tumor Necrosis Factor-alpha - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:It has been known that the expression of inducible nitric oxide synthase (iNOS) is up-regulated during hepatic regeneration. The present study characterized the molecular mechanisms involved in the transcriptional activation of iNOS gene by using the serum after partial hepatectomy (post-PH serum) in vitro. The post-PH serum rapidly induced iNOS mRNA expression, which was blocked by anti-tumor necrosis factor-α (TNF-α) antibody in BNL CL.2 cells, murine embryonic liver cell line. In addition, EMSAs using a NF-κB-specific oligomer showed that the up-regulated iNOS mRNA expression in cells treated with post-PH serum correlated with transient activation of NF-κB complex (p50/p65 heterodimer). Transient transfection of BNL CL.2 cells with iNOS promoter linked to a CAT reporter gene showed the transcriptional activation of iNOS promoter by post-PH serum. Furthermore, site-directed mutational analysis of the two NF-κB sites individually or in combination revealed that iNOS expression by post-PH serum is regulated by the downstream NF-κB site, but not by upstream NF-κB site. Taken together, these results suggest that the downstream NF-κB site acts as an essential component for the iNOS expression by post-PH serum during hepatic regeneration.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2001.5034