Mitochondrial NOS upregulation during renal I/R causes apoptosis in a peroxynitrite-dependent manner.
In the last decade, various groups have found evidence of nitric oxide production by mitochondrial nitric oxide synthase (mNOS) in a range of experimental models. However, little is known about the role of mNOS in renal ischemia-reperfusion (I/R) injury and its possible involvement in the apoptotic pathway. We analyzed the role of mNOS in apoptosis promotion in rat kidney I/R and its direct implication through experiments in which isolated kidney mitochondria were subjected to hypoxia/reoxygenation. Results showed that neuronal NOS located in the inner mitochondrial membrane is upregulated during renal I/R and that this upregulation, together with the increase in nitric oxide production, is involved in the generation of intramitochondrial peroxynitrite, which in turn leads to cytochrome c release and apoptosis induction in renal I/R.
Department of Experimental Pathology, Instituto de Investigaciones Biomédicas, IIBB-CSIC, IDIBAPS, Barcelona, Spain.
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D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D015153:Blotting, Western; D045304:Cytochromes c / Q000378:metabolism; D003720:Densitometry; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007511:Ischemia / Q000209:etiology / Q000378:metabolism*; D007668:Kidney / Q000098:blood supply; D008297:Male; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
D015415:Biomarkers; D004791:Enzyme Inhibitors; D009573:Nitrites; D030421:Peroxynitrous Acid; D045304:Cytochromes c; D052248:Nitric Oxide Synthase Type I; D019331:NG-Nitroarginine Methyl Ester