Extracellular Superoxide Dismutase Protects against... : Journal of the American Society of Nephrology (original) (raw)

Basic Research

Extracellular Superoxide Dismutase Protects against Proteinuric Kidney Disease

Tan, Roderick J.*; Zhou, Dong†; Xiao, Liangxiang‡; Zhou, Lili‡; Li, Yingjian†; Bastacky, Sheldon I.†; Oury, Tim D.†; Liu, Youhua†,‡

Departments of *Medicine and

†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

Correspondence: Dr. Youhua Liu, Department of Pathology, University of Pittsburgh School of Medicine, S-405 Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15261. Email: [email protected]

Received June 25, 2014

Accepted December 9, 2014

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.