Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury.
Protective role of extracellular superoxide dismutase in renal ischemia/reperfusion injury.
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DOI：
10.1038/ki.2010.141
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发表时间：
2010-08
影响因子：
19.6
通讯作者：
Pollock, Jennifer S.
中科院分区：
文献类型：
--
作者：
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.
细胞外超氧化物歧化酶(SOD3)在肾组织中高表达，是血管功能的重要调节因子。我们假设SOD3的缺失将延缓肾血流量的恢复，增加肾缺血/再灌注后的氧化应激和损伤。对雄性和雌性野生型(WT)和SOD3基因敲除(−/−)小鼠肾皮质匀浆中超氧化物歧化酶(SOD3)亚型的表达和活性、基础超氧化物歧化产物和NADPH氧化酶活性进行了研究。在单侧缺血60分钟后，我们使用超声血流探头(Transonic)和组织学方法评估缺血后肾脏的氧化应激和损伤。雄鼠SOD3−/−较WT小鼠总超氧化物歧化酶活性降低(7.4±0.3vs12.6±1.7U/ml，p=0.0 1)。然而，雌性SOD3−/−小鼠和WT小鼠的总超氧化物歧化酶活性相似(14.2±1.4vs16.3±1.8U/ml，N.S.)，提示SOD1活性上调。女性SOD3SOD3−/−的基础超氧物生成量显著高于WT同龄人，但男性并不明显。WT和SOD3型−/−小鼠的NADPH氧化酶活性相似。与WT小鼠相比，SOD3SOD3−/−雄性小鼠肾脏缺血后的肾脏血流量减少，但雌性小鼠没有。24小时后，雄性和雌性SOD3−/−小鼠的肾脏表现出比WT小鼠更多的氧化应激(3-硝基酪氨酸染色)和肾脏管型形成。SOD3的缺失对雄性小鼠肾缺血后再灌流有损害作用，但对雌性小鼠无影响，这与雌性小鼠肾缺血后总超氧化物歧化酶活性的保存有关。然而，无论男女，SOD3缺失都会增加缺血后的氧化应激和损伤，这表明SOD3在肾脏缺血/再灌注损伤中起着关键作用。
Extracellular superoxide dismutase (SOD3) is highly expressed in renal tissues and an important regulator of vascular function. We hypothesized that deletion of SOD3 will attenuate recovery of renal blood flow and increase oxidative stress and injury following renal ischemia/reperfusion. Expression and activities of SOD isoforms, basal superoxide production, and NADPH oxidase activity were evaluated in renal cortical homogenates from male and female wild-type (WT) and SOD3-knockout (SOD3−/−) mice. After 60 minutes of unilateral ischemia, we assessed renal reperfusion using an ultrasonic flow probe (Transonic) and histological measures of oxidative stress and injury in the post-ischemic kidneys. Total SOD activity was reduced in male SOD3−/− versus WT mice (7.4±0.3 vs 12.6±1.7 U/ml, p=0.01). However, total SOD activity was similar in female SOD3−/− versus WT mice (14.2±1.4 vs 16.3±1.8 U/ml, n.s.), suggesting up-regulated SOD1 activity. Basal superoxide production was significantly higher in female SOD3−/− versus WT counterparts, but not male. NADPH oxidase activity was similar in WT and SOD3−/− mice. Compared to WT mice, renal blood flow after ischemia was attenuated in kidneys from male, but not female, SOD3−/− mice. After 24 hours, kidneys from male and female SOD3−/− mice demonstrated more oxidative stress (3-nitrotyrosine staining) and renal cast formation than those from WT mice. Loss of SOD3 impairs reperfusion after renal ischemia in male but not in female mice, which is associated with preserved total SOD activity in females. Yet, SOD3 deletion increases post-ischemic oxidative stress and injury in both sexes, demonstrating a key role for SOD3 in renal ischemia/reperfusion injury.
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影响因子：
4.8
作者：
Kim, Jinu;Kil, In Sup;Park, Kwon Moo
通讯作者：
Park, Kwon Moo
影响因子：
13.6
作者：
Perianayagam, Mary C.;Liangos, Orfeas;Jaber, Bertrand L.
通讯作者：
Jaber, Bertrand L.
影响因子：
8.3
作者：
Sullivan, JC;Pollock, DM;Pollock, JS
通讯作者：
Pollock, JS
影响因子：
19.6
作者：
LINAS, SL;WHITENBURG, D;REPINE, JE
通讯作者：
REPINE, JE
DOI：
10.1152/ajpcell.1998.275.3.c840
发表时间：
1998-09-01
影响因子：
5.5
作者：
Ookawara, T;Imazeki, N;Ohno, H
通讯作者：
Ohno, H