Role of the Transcription Factor BTB and CNC Homology 1 in a Rat Model of Acute Liver Injury Induced by Experimental Endotoxemia

Nohito Tanioka, Hiroko Shimizu, Emiko Omori, Toru Takahashi, Masakazu Yamaoka, Hiroshi Morimatsu

Research output: Contribution to journalArticlepeer-review

Abstract

Hepatic oxidative stress plays an important role in the pathogenesis of several acute liver diseases, and free heme is thought to contribute to endotoxemia-induced acute liver injury. The heme oxygenase 1 (HO-1) gene is upregulated and the δ-aminolevulinate synthase (ALAS1) gene is downregulated in the rat liver following lipopolysaccharide (LPS) treatment. BTB and CNC homology 1 (Bach1) is a heme-responsive transcription factor that normally represses HO-1 expression. In this study, we evaluated the changes in HO-1, ALAS1, and Bach1 expression and nuclear Bach1 expression in rat livers following intravenous LPS administration (10 mg/kg body weight). LPS significantly upregulated HO-1 mRNA and downregulated ALAS1 mRNA in the rat livers, suggesting that hepatic free heme concentrations are increased after LPS treatment. Bach1 mRNA was strongly induced after LPS injection. In contrast, nuclear Bach1 was significantly but transiently decreased after LPS treatment. Rats were also administered hemin (50 mg/kg body weight) intravenously to elevate heme concentrations, which decreased nuclear Bach1 levels. Our results suggest that elevated hepatic free heme may be associated with a decline of nuclear Bach1, and induction of Bach1 mRNA may compensate for the decreased nuclear Bach1 after LPS treatment in the rat liver.

Original languageEnglish
Pages (from-to)363-372
Number of pages10
JournalActa medica Okayama
Volume75
Issue number3
Publication statusPublished - 2021

Keywords

  • BTB and CNC homology 1
  • heme
  • heme oxygenase-1
  • lipopolysaccharide
  • liver injury

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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