Oncotarget

Research Papers:

MnTBAP therapy attenuates the downregulation of sodium transporters in obstructive kidney disease

Mi Liu, Yangyang Zhu, Ying Sun, Zhaoying Wen, Songming Huang, Guixia Ding, Aihua Zhang, Zhanjun Jia _ and Yue Zhang

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Oncotarget. 2018; 9:394-403. https://doi.org/10.18632/oncotarget.23037

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Abstract

Mi Liu1,2, Yangyang Zhu1,4, Ying Sun1,4, Zhaoying Wen5, Songming Huang1,3, Guixia Ding1,3, Aihua Zhang1,3, Zhanjun Jia1,3 and Yue Zhang1,3

1Nanjing Key Laboratory of Pediatrics, Children’s Hospital of Nanjing Medical University, Nanjing, China

2Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China

3Department of Nephrology, Children’s Hospital of Nanjing Medical University, Nanjing, China

4Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China

5Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China

Correspondence to:

Zhanjun Jia, email: [email protected]

Yue Zhang, email: [email protected]

Keywords: unilateral ureteral obstruction; mitochondrial oxidative stress; sodium transporters; MnTBAP; SOD

Received: July 18, 2017     Accepted: November 13, 2017     Published: December 07, 2017

ABSTRACT

Ureteral obstruction is associated with reduced expressions of renal sodium transporters, which contributes to impaired urinary concentrating capacity. In this study, we employed a synthetic mitochondrial superoxide dismutase 2 (SOD2) mimic MnTBAP to investigate the role of mitochondrial oxidative stress in modulating the sodium transporters in obstructive kidney disease. Following unilateral ureteral obstruction (UUO) for 7 days, a global reduction of sodium transporters including NHE3, NCC, NKCC2, and ENaCα was observed as determined by qRT-PCR, Western Blotting or immunohistochemistry. Among these sodium transporters, the downregulation of NHE3, NCC, and NKCC2 was partially reversed by MnTBAP treatment. In contrast, the reduction of ENaCα was not affected by MnTBAP. The β and γ subunits of ENaC were not significantly altered by ureteral obstruction or MnTBAP therapy. To further confirm the anti-oxidant effect of MnTBAP, we examined the levels of TBARs in the urine collected from the obstructed ureters of UUO mice and bladder of sham mice. As expected, the increment of urinary TBARs in UUO mice was entirely abolished by MnTBAP therapy, indicating an amelioration of oxidative stress. Meantime, we found that three types of SOD were all reduced in obstructed kidneys determined by qRT-PCR, which was unaffected by MnTBAP. Collectively, these results demonstrated an important role of mitochondrial oxidative stress in mediating the downregulation of sodium transporters in obstructive kidney disease.


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