Role of metabolic intermediates in lipopolysaccharide/cytokine-mediated production of nitric oxide in isolated mouse hepatocytes

Jun F. Liang, Toshihiro Akaike

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Induction of nitric oxide synthase by bacterial endotoxin in vivo can be mimicked by treating cultured hepatocytes with a combination of lipopolysaccharide and cytokines (LPS/cytokines), but the role of LPS/cytokine-induced nitric oxide in hepatocyte glucose metabolism is ambiguous. In this study, intermediary metabolite effects on LPS/cytokine-induced hepatocyte nitric oxide synthesis were examined. Pyruvate, lactate, oxaloacetate, and fumarate all showed some inhibitory effects on hepatocyte nitric oxide synthesis. However, these metabolic intermediates could not improve the mitochondrial respiration of LPS/cytokine-treated hepatocytes. Phosphoenolpyruvate carboxykinase activity (or flux) relating factors, glucocorticoids and cAMP, also blocked LPS/cytokine-induced nitric oxide synthesis. Insulin was much less potent than cAMP and glucocorticoids, and phorbol ester did not show any effect on hepatocyte nitric oxide synthesis. These results suggest that LPS/cytokine-induced nitric oxide synthesis is related, at least partly, to phosphoenolpyruvate carboxykinase activity (or flux) in hepatocytes.

Original languageEnglish
Pages (from-to)379-382
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume236
Issue number2
DOIs
StatePublished - 18 Jul 1997

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