Mitochondrial electron transport inhibition in full genomic hepatitis C virus replicon cells is restored by reducing viral replication

Mie Ando, Masaaki Korenaga, Keisuke Hino, Masanori Ikeda, Nobuyuki Kato, Sohji Nishina, Isao Hidaka, Isao Sakaida

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background/Aim: Hepatitis C virus (HCV) core protein has been shown to inhibit mitochondrial electron transport and to increase reactive oxygen species (ROS) in vitro and in vivo. The aim of this study was to investigate whether inhibiting HCV replication could restore the mitochondrial redox state and electron transport activity. Methods: We measured ROS, mitochondrial reduced glutathione content, and mitochondrial complex I, II, III and IV activities and protein expression in full genomic HCV replicon cells and cured cells that had been prepared by eliminating HCV RNA from replicon cells by interferon (IFN)-α treatment. Results: Cured cells had significantly lower ROS production and greater mitochondrial glutathione content than replicon cells. Complete inhibition of HCV replication by IFN-α restored complex I and IV activities by 20-30% (P < 0.01) and complex I expression (P < 0.05). Treatment with fluvastatin, one of the 3-hydroxy-3-methylglutaryl co-enzyme A reductase inhibitors, which is known to have anti-HCV activity, partially inhibited core protein expression and restored complex I activity in full genomic HCV replicon cells to a lesser degree (P < 0.05). Conclusions: Our results show that the mitochondrial redox state and electron transport activity can be restored by reducing HCV replication.

Original languageEnglish
Pages (from-to)1158-1166
Number of pages9
JournalLiver International
Volume28
Issue number8
DOIs
Publication statusPublished - 2008

Keywords

  • Fluvastatin
  • Interferon
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Hepatology

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