title: The cytoprotective effect of nitrite is based on the formation of dinitrosyl iron complexes.
abstract: Nitrite protects various organs from ischemia-reperfusion injury by ameliorating mitochondrial dysfunction. Here we provide evidence that this protection is due to the inhibition of iron-mediated oxidative reactions caused by the release of iron ions upon hypoxia. We show in a model of isolated rat liver mitochondria that upon hypoxia, mitochondria reduce nitrite to nitric oxide (NO) in amounts sufficient to inactivate redox-active iron ions by formation of inactive dinitrosyl iron complexes (DNIC). The scavenging of iron ions in turn prevents the oxidative modification of the outer mitochondrial membrane and the release of cytochrome c during reoxygenation. This action of nitrite protects mitochondrial function. The formation of DNIC with nitrite-derived NO could also be confirmed in an ischemia-reperfusion model in liver tissue. Our data suggest that the formation of DNIC is a key mechanism of nitrite-mediated cytoprotection.
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, A-1200 Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Dungel
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, A-1200 Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Perlinger
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, A-1200 Vienna, Austria.
authors.forename: Adelheid
authors.initials: A
authors.lastname: Weidinger
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, A-1200 Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, Austrian Cluster for Tissue Regeneration, A-1200 Vienna, Austria. Electronic address: andrey.kozlov@trauma.lbg.ac.at.
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kozlov
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D019610:Cytoprotection; D005978:Glutathione / Q000378:metabolism; D000860:Hypoxia; D007501:Iron / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000494:pharmacology*; D009589:Nitrogen Oxides / Q000378:metabolism*; D051381:Rats; D015427:Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D009573:Nitrites; D009589:Nitrogen Oxides; D009569:Nitric Oxide; C073661:dinitrosyl iron complex; D007501:Iron; D005978:Glutathione
keywords: Cytochrome c; Cytoprotection; Iron ions; Lipid peroxidation; Mitochondria; Nitrite; Rats