The Ca2+ second messenger system and interleukin-1-alpha modulation of hepatic gene transcription and mitochondrial fat oxidation

R. A. Barke, P. S. Brady, L. J. Brady

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Cytokines have been implicated in the modulation of fat metabolism after sepsis. Carnitine palmitoyltransferase (CPT), the regulatory enzyme of hepatic mitochondrial long-chain fatty-acid oxidation, is involved in the control of hepatic fat oxidation in sepsis. Using either H4IIe rat hepatoma cells or rat hepatocytes in primary culture, we tested the hypothesis that interleukin-1-alpha (IL-1α) would modulate CPT transcription (CPT mRNA), CPT translation (35S-methionine CPT protein incorporation), and hepatic mitochondrial oxidation of 1-Carbon 14-labeled (14C) palmitate to ketone bodies (acid soluble products). We showed that IL-1α significantly increased CPT mRNA, 35S-methionine incorporation CPT protein, and hepatic mitochondrial oxidation of 1-14C-palmitate to acid soluble products. We further hypothesized that the Ca2+ second messenger system may play a role in the IL-1α induction of hepatic CPT gene transcription. We showed that either calcium ionophore (A23187) or phorbol myristate acetate increased CPT gene transcription and that either calcium chelation, protein kinase C inhibition (acridine orange), or chronic exposure to phorbol myristate acetate significantly inhibited IL-1α induction of CPT mRNA. We conclude that the IL-1α increases in hepatic mitochondrial fatty-acid oxidation may be, in part, secondary to increased CPT gene transcription and translation and that the Ca2+ second messenger system may play in important role in IL- 1α induction of CPT gene transcription.

Original languageEnglish (US)
Pages (from-to)285-294
Number of pages10
JournalSurgery
Volume110
Issue number2
StatePublished - 1991

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