Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury

Markus P. Schneider, Jennifer C Sullivan, Paul F. Wach, Erika I. Boesen, Tatsuo Yamamoto, Tohru Fukai, David G. Harrison, David M. Pollock, Jennifer S. Pollock

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)374-381
Number of pages8
JournalKidney International
Volume78
Issue number4
DOIs
StatePublished - Jan 1 2010

Fingerprint

Reperfusion Injury
Superoxide Dismutase
Kidney
Renal Circulation
Knockout Mice
Oxidative Stress
Ischemia
NADP
Superoxides
Oxidoreductases
Wounds and Injuries
Ultrasonics
Reperfusion
Blood Vessels
Immunohistochemistry
Genotype

Keywords

  • ischemia
  • oxidative stress
  • renal circulation
  • reperfusion injury
  • superoxide
  • superoxide dismutase

ASJC Scopus subject areas

  • Nephrology

Cite this

Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury. / Schneider, Markus P.; Sullivan, Jennifer C; Wach, Paul F.; Boesen, Erika I.; Yamamoto, Tatsuo; Fukai, Tohru; Harrison, David G.; Pollock, David M.; Pollock, Jennifer S.

In: Kidney International, Vol. 78, No. 4, 01.01.2010, p. 374-381.

Research output: Contribution to journalArticle

Schneider, MP, Sullivan, JC, Wach, PF, Boesen, EI, Yamamoto, T, Fukai, T, Harrison, DG, Pollock, DM & Pollock, JS 2010, 'Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury', Kidney International, vol. 78, no. 4, pp. 374-381. https://doi.org/10.1038/ki.2010.141
Schneider, Markus P. ; Sullivan, Jennifer C ; Wach, Paul F. ; Boesen, Erika I. ; Yamamoto, Tatsuo ; Fukai, Tohru ; Harrison, David G. ; Pollock, David M. ; Pollock, Jennifer S. / Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury. In: Kidney International. 2010 ; Vol. 78, No. 4. pp. 374-381.
@article{73cf9c5dc02e4e798cd9465f9d8d5e18,
title = "Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury",
abstract = "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.",
keywords = "ischemia, oxidative stress, renal circulation, reperfusion injury, superoxide, superoxide dismutase",
author = "Schneider, {Markus P.} and Sullivan, {Jennifer C} and Wach, {Paul F.} and Boesen, {Erika I.} and Tatsuo Yamamoto and Tohru Fukai and Harrison, {David G.} and Pollock, {David M.} and Pollock, {Jennifer S.}",
year = "2010",
month = "1",
day = "1",
doi = "10.1038/ki.2010.141",
language = "English (US)",
volume = "78",
pages = "374--381",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury

AU - Schneider, Markus P.

AU - Sullivan, Jennifer C

AU - Wach, Paul F.

AU - Boesen, Erika I.

AU - Yamamoto, Tatsuo

AU - Fukai, Tohru

AU - Harrison, David G.

AU - Pollock, David M.

AU - Pollock, Jennifer S.

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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.

AB - 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.

KW - ischemia

KW - oxidative stress

KW - renal circulation

KW - reperfusion injury

KW - superoxide

KW - superoxide dismutase

UR - http://www.scopus.com/inward/record.url?scp=77955174380&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77955174380&partnerID=8YFLogxK

U2 - 10.1038/ki.2010.141

DO - 10.1038/ki.2010.141

M3 - Article

VL - 78

SP - 374

EP - 381

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 4

ER -