Carbon Monoxide Protects against Liver Failure through Nitric Oxide-induced Heme Oxygenase 1 Academic Article uri icon


MeSH Major

  • Carbon Monoxide
  • Heme Oxygenase (Decyclizing)
  • Liver Failure
  • Nitric Oxide


  • Carbon monoxide (CO) and nitric oxide (NO) each have mechanistically unique roles in various inflammatory disorders. Although it is known that CO can induce production of NO and that NO can induce expression of the cytoprotective enzyme heme oxygenase 1 (HO-1), there is no information whether the protective effect of CO ever requires NO production or whether either gas must induce expression of HO-1 to exert its functional effects. Using in vitro and in vivo models of tumor necrosis factor alpha-induced hepatocyte cell death in mice, we find that activation of nuclear factor kappaB and increased expression of inducible NO are required for the protective effects of CO, whereas the protective effects of NO require up-regulation of HO-1 expression. When protection from cell death is initiated by CO, NO production and HO-1 activity are each required for the protective effect showing for the first time an essential synergy between these two molecules in tandem providing potent cytoprotection.

publication date

  • December 2003



  • Academic Article



  • eng

PubMed Central ID

  • PMC2194127

Digital Object Identifier (DOI)

  • 10.1084/jem.20031003

PubMed ID

  • 14657222

Additional Document Info

start page

  • 1707

end page

  • 16


  • 198


  • 11