Developmental variability in expression and regulation of inducible nitric oxide synthase in rat intestine

Inducible nitric oxide synthase (iNOS) may be a key mediator of intestinal injury, which varies with developmental age. One member of the mitogen-activated protein kinase (MAPK) family, p38, is involved in the lipopolysaccharide (LPS)-mediated iNOS induction. The involvement of p38 MAPK in basal and...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology: Gastrointestinal and liver physiology 2001-08, Vol.281 (2), p.G552-G559
Main Authors: Morin, M J, Karr, S M, Faris, R A, Gruppuso, P A
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Enzyme Inhibitors - pharmacology
Female
Gene Expression Regulation, Developmental
Ileum - growth & development
Ileum - metabolism
Imidazoles - pharmacology
Lipopolysaccharides - pharmacology
Liver - growth & development
Liver - metabolism
Male
Mitogen-Activated Protein Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinases - metabolism
Nitric Oxide Synthase - biosynthesis
Nitric Oxide Synthase - genetics
Nitric Oxide Synthase Type II
p38 Mitogen-Activated Protein Kinases
Pyridines - pharmacology
Rats
Rats, Sprague-Dawley
RNA, Messenger - biosynthesis
Sex Factors
Up-Regulation
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:Inducible nitric oxide synthase (iNOS) may be a key mediator of intestinal injury, which varies with developmental age. One member of the mitogen-activated protein kinase (MAPK) family, p38, is involved in the lipopolysaccharide (LPS)-mediated iNOS induction. The involvement of p38 MAPK in basal and LPS-induced iNOS expression was examined in the rat intestine at two developmental ages. Neonatal (4 days postnatal) and adolescent (15 days postnatal) rats were injected with LPS (5 microg/g ip), a selective p38 inhibitor (SB 203580), or both. Tissue was removed after 4 h and 6 h for mRNA and protein analysis. iNOS mRNA and protein were markedly upregulated in the adolescent female following LPS exposure, whereas males had an attenuated response. Neonates had a minimal response. SB 203580 suppressed LPS-induced iNOS mRNA and protein in the ileum, more so in females than in males. Adolescent ileal p38 activation was constitutively high and nonresponsive to LPS. Basal and post-LPS p38 phosphorylation was low in neonatal ileum. We conclude that ileal iNOS expression is developmentally regulated and influenced by gender and that p38 is permissive for LPS effect. The developmental regulation of p38 may contribute to age-dependent variations of intestinal injury.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.2001.281.2.g552