The role of mitochondria in oxidative and nitrosative stress during ischemia/reperfusion in the rat kidney.
Reoxygenation following ischemia causes tissue oxidative stress. We studied the role of oxidative stress caused by kidney ischemia/reperfusion (I/R) on the mitochondria of renal tissue slices. I/R caused the mitochondria to be swollen, fragmented, and have lower membrane potential. The mitochondria generated more reactive oxygen species (ROS) and nitric oxide (NO) in situ as measured by fluorescence of ROS- and NO-sensitive probes. Infusion of lithium ion, an inhibitor of glycogen kinase synthase-3, caused phosphorylation of its Ser-9 and restored the membrane potential and decreased ROS production of the mitochondrial fraction. Ischemic kidney and hypoxic rat preconditioning improved mitochondrial membrane potential and lowered ROS production caused by subsequent I/R similar to lithium ion infusion. Preconditioning normalized NO production in mitochondria as well. The drop in the mitochondrial membrane potential was prevented by NO synthase inhibition, demonstrating a strong contribution of NO to changes in mitochondrial energy metabolism during the I/R transition. Mitochondria in the I/R-stressed kidney contained less cytochrome c and more pro-apoptotic Bax, consistent with apoptotic degradation.
Plotnikov
E Y
EY
Laboratory of Mitochondrial Structure and Functions, AN Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
Kazachenko
A V
AV
Vyssokikh
M Y
MY
Vasileva
A K
AK
Tcvirkun
D V
DV
Isaev
N K
NK
Kirpatovsky
V I
VI
Zorov
D B
DB
D000818:Animals; D021461:Animals, Outbred Strains; D017209:Apoptosis / Q000502:physiology; D004579:Electron Transport / Q000502:physiology; D004734:Energy Metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D019194:Ischemic Preconditioning; D007672:Kidney Cortex / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D008094:Lithium / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
D004791:Enzyme Inhibitors; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D008094:Lithium; D038362:Glycogen Synthase Kinase 3