Hepatocellular HO-1 mediated iNOS-induced hepatoprotection against liver ischemia reperfusion injury

Biochem Biophys Res Commun. 2020 Jan 22;521(4):1095-1100. doi: 10.1016/j.bbrc.2019.11.053. Epub 2019 Nov 14.

Abstract

Hepatocyte-derived inducible nitric oxide synthase (iNOS) was proved to impart protection against liver ischemia reperfusion (I/R) injury in our prior analysis. However, the mechanism for this hepatoprotection remains incompletely understood. Bone marrow chimeric mice were generated using expression of iNOS in a hepatocyte-selective manner against an iNOS-knockout background. The function of heme oxygenase 1 (HO-1) in iNOS-stimulated hepatoprotection and the molecular mechanisms were explored in vitro and in vivo, respectively. Hepatocyte-derived iNOS conferred protection from I/R injury and anoxia/reoxygenation stimulation. Mechanistically, iNOS activated nuclear factor erythroid 2-related factor 2 (Nrf-2) and subsequently, stimulated the transcription of HO-1. Results from our study led to the conclusion that HO-1 is another potent mediator of iNOS-mediated protection after liver I/R.

Keywords: HO-1; Liver; Reperfusion injury; iNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Cells, Cultured
  • Heme Oxygenase-1 / metabolism*
  • Hepatocytes / enzymology*
  • Liver / pathology*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • NF-E2-Related Factor 2 / metabolism
  • Nitric Oxide Synthase Type II / metabolism*
  • Protein Transport
  • Reperfusion Injury / enzymology*
  • Reperfusion Injury / pathology*
  • Up-Regulation / genetics

Substances

  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Nitric Oxide Synthase Type II
  • Heme Oxygenase-1