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Inhibition of Mitochondrial Complex-1 Prevents the Downregulation of NKCC2 and ENaC? in Obstructive Kidney Disease.


ABSTRACT: Ureteral obstruction with subsequent hydronephrosis is a common clinical complication. Downregulation of renal sodium transporters in obstructed kidneys could contribute to impaired urinary concentrating capability and salt waste following the release of a ureteral obstruction. The current study was undertaken to investigate the role of mitochondrial complex-1 inhibition in modulating sodium transporters in obstructive kidney disease. Following unilateral ureteral obstruction (UUO) for 7 days, a global reduction of sodium transporters, including NHE3, ?-Na-K-ATPase, NCC, NKCC2, p-NKCC2, ENaC?, and ENaC?, was observed, as determined via qRT-PCR and/or Western blotting. Interestingly, inhibition of mitochondrial complex-1 by rotenone markedly reversed the downregulation of NKCC2, p-NKCC2, and ENaC?. In contrast, other sodium transporters were not affected by rotenone. To study the potential mechanisms involved in mediating the effects of rotenone on sodium transporters, we examined a number of known sodium modulators, including PGE2, ET1, Ang II, natriuretic peptides (ANP, BNP, and CNP), and nitric oxide synthases (iNOS, nNOS, and eNOS). Importantly, among these modulators, only BNP and iNOS were significantly reduced by rotenone treatment. Collectively, these findings demonstrated a substantial role of mitochondrial dysfunction in mediating the downregulation of NKCC2 and ENaC? in obstructive kidney disease, possibly via iNOS-derived nitric oxide and BNP.

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC4513566 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Inhibition of Mitochondrial Complex-1 Prevents the Downregulation of NKCC2 and ENaCα in Obstructive Kidney Disease.

Zhang Yue Y   Sun Ying Y   Ding Guixia G   Huang Songming S   Zhang Aihua A   Jia Zhanjun Z  

Scientific reports 20150724


Ureteral obstruction with subsequent hydronephrosis is a common clinical complication. Downregulation of renal sodium transporters in obstructed kidneys could contribute to impaired urinary concentrating capability and salt waste following the release of a ureteral obstruction. The current study was undertaken to investigate the role of mitochondrial complex-1 inhibition in modulating sodium transporters in obstructive kidney disease. Following unilateral ureteral obstruction (UUO) for 7 days, a  ...[more]

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