Mitochondrial targets of oxidative stress during renal ischemia/reperfusion.
Endogenous tyrosine nitration and inactivation of manganese superoxide dismutase (MnSOD) has previously been shown to occur in both human and rat chronic renal allograft rejection. To elucidate the time course of MnSOD inactivation and mitochondrial dysfunction at earlier times during renal transplantation, we developed a rodent model of renal ischemia/reperfusion (I/R). Renal function was significantly impaired at 16 h reperfusion following 30 min of warm ischemia. Tyrosine nitration of specific mitochondrial proteins, MnSOD and cytochrome c, occurred at the earliest time point examined, an event that preceded significant renal injury. Interestingly, a small percentage of both mitochondrial proteins were also located in the cytosol. This leakage and decreased adenosine 5(')-triphosphate levels indicate loss of mitochondrial membrane integrity during renal I/R. Inactivation of MnSOD occurred rapidly in this model of renal I/R, suggesting that loss of MnSOD activity leads to further renal injury and nitration of other mitochondrial targets.
Cruthirds
Danielle L
DL
Department of Pharmacology, UAB School of Medicine, Birmingham, AL 35294, USA.
Novak
Lea
L
Akhi
Kabir M
KM
Sanders
Paul W
PW
Thompson
John A
JA
MacMillan-Crow
Lee Ann
LA
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D003404:Creatinine / Q000097:blood; D003574:Cytochrome c Group / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D007511:Ischemia; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D018384:Oxidative Stress; D011233:Precipitin Tests; D051381:Rats; D011916:Rats, Inbred F344; D015427:Reperfusion Injury; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D003574:Cytochrome c Group; D016877:Oxidants; C002744:3-nitrotyrosine; D014443:Tyrosine; D000255:Adenosine Triphosphate; D003404:Creatinine; D013482:Superoxide Dismutase