title: Extracellular Superoxide Dismutase Protects against Proteinuric Kidney Disease.
abstract: Extracellular superoxide dismutase (EC-SOD), also known as SOD3, is an antioxidant expressed at high levels in normal adult kidneys. Because oxidative stress contributes to a variety of kidney injuries, we hypothesized that EC-SOD may be protective in CKD progression. To study this hypothesis, we used a murine model of ADR nephropathy characterized by albuminuria and renal dysfunction. We found that levels of EC-SOD diminished throughout the course of disease progression and were associated with increased levels of NADPH oxidase and oxidative stress markers. EC-SOD null mice were sensitized to ADR injury, as evidenced by increases in albuminuria, serum creatinine, histologic damage, and oxidative stress. The absence of EC-SOD led to increased levels of NADPH oxidase and an increase in β-catenin signaling, which has been shown to be pathologic in a variety of kidney injuries. Exposure of EC-SOD null mice to either chronic angiotensin II infusion or to daily albumin injections also caused increased proteinuria. In contrast, EC-SOD null mice subjected to nonproteinuric CKD induced by unilateral ureteral obstruction exhibited no differences compared with wild-type mice. Finally, we also found a decrease in EC-SOD in human CKD biopsy samples, similar to our findings in mice. Therefore, we conclude that EC-SOD is protective in CKDs characterized by proteinuria.
authors: Departments of Medicine and.
authors: Roderick J
authors: RJ
authors: Tan
authors: Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
authors: Dong
authors: D
authors: Zhou
authors: Division of Nephrology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Liangxiang
authors: L
authors: Xiao
authors: Division of Nephrology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors: Lili
authors: L
authors: Zhou
authors: Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
authors: Yingjian
authors: Y
authors: Li
authors: Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
authors: Sheldon I
authors: SI
authors: Bastacky
authors: Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and.
authors: Tim D
authors: TD
authors: Oury
authors: Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; and Division of Nephrology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, China liuy@upmc.edu.
authors: Youhua
authors: Y
authors: Liu
mesh_terms: D000818:Animals; D004317:Doxorubicin / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011507:Proteinuria / Q000139:chemically induced / Q000517:prevention & control*; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000502:physiology* / Q000627:therapeutic use*
chemical_list: D004317:Doxorubicin; C499090:Sod3 protein, mouse; D013482:Superoxide Dismutase
keywords: kidney disease; oxidative stress; podocyte; proteinuria
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