Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury.
Extracellular superoxide dismutase (SOD3) is highly expressed in renal tissues and a critical regulator of vascular function. We hypothesized that deletion of SOD3 would attenuate recovery of renal blood flow (RBF) and increase oxidative stress and injury following renal ischemia/reperfusion (I/R). To test this, we evaluated SOD expression and activity, basal superoxide production, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity in kidneys from male and female wild-type (WT) and SOD3-knockout mice. RBF, measured using an ultrasonic flow probe, and histological indices of oxidative stress and injury were assessed after 1 h of ischemia. Following ischemia, RBF was attenuated in kidneys from male, but not female, knockout mice compared with their WT counterparts. Total SOD activity was significantly reduced in male knockout compared with WT male mice but was similar in female mice of both genotypes, suggesting upregulated SOD1 activity. Basal superoxide production and NADPH oxidase activity were unrelated to the differences in RBF. After 24 h, kidneys from both genders of knockout mice were found to have more oxidative stress (3-nitrotyrosine immunohistochemistry) and renal cast formation than those from WT mice. Thus, our study found a key role for SOD3 in regulating renal I/R injury.
Schneider
Markus P
MP
Vascular Biology Center, Medical College of Georgia, Augusta, Georgia, USA.
Sullivan
Jennifer C
JC
Wach
Paul F
PF
Boesen
Erika I
EI
Yamamoto
Tatsuo
T
Fukai
Tohru
T
Harrison
David G
DG
Pollock
David M
DM
Pollock
Jennifer S
JS
D000818:Animals; D005260:Female; D007674:Kidney Diseases; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress; D012039:Regional Blood Flow; D015427:Reperfusion Injury; D012737:Sex Factors; D013482:Superoxide Dismutase / Q000172:deficiency / Q000502:physiology*
C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase; D019255:NADPH Oxidases