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The cytoprotective effect of nitrite is based on the formation of dinitrosyl iron complexes |
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| Affiliation: | 1. Institute of Chemistry, Jan Kochanowski University, 15G Świętokrzyska Str., 25-406 Kielce, Poland;2. Institute of Low Temperature and Structure Research, Polish Academy of Sciences, Okólna 2, 50-950 Wrocław, Poland;3. Institute of Molecular Physics, Polish Academy of Sciences, 60-179 Poznań, Poland;1. Department of Chemistry, 315 S. 1400 E. RM 2124, University of Utah, Salt Lake City, UT 84112-0850, USA;2. Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093-0358, USA;3. Material Research Science and Engineering Center, University of Utah, Salt Lake City, UT 84112, USA;1. Molecular and Clinical Pharmacology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago-7, Chile;2. School of Medical Technology, Faculty of Health and Odontology, Diego Portales University, Santiago, Chile;3. Department of Medical Technology, Faculty of Medicine, University of Chile, Santiago-7, Chile |
| 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. |
| Keywords: | Mitochondria Rats Iron ions Nitrite Cytoprotection Lipid peroxidation Cytochrome c |
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