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Inhibition of Mitochondrial complex-1 Restores the Downregulation of Aquaporins in Obstructive Nephropathy

Inhibition of Mitochondrial complex-1 Restores the Downregulation of Aquaporins in Obstructive Nephropathy

Ying Sun, Yue Zhang, Yangyang Zhu, Aihua Zhang, Songming Huang, Xiaoxin Yin, Guixia Ding, Mi Liu, Zhanjun Jia

Am J Physiol Renal Physiol. 2016 Oct 1;311(4):F777-F786.

PMID: 27413198

Abstract:

Obstructive kidney disease is a common complication in the clinic. Downregulation of aquaporins (AQPs) in obstructed kidneys has been thought as a key factor leading to the polyuria and impairment of urine-concentrating capability after the release of kidney obstruction. The present study was to investigate the role of mitochondrial complex-1 in modulating AQPs in obstructive nephropathy. Following 7-day unilateral ureteral obstruction (UUO), AQP1, AQP2, AQP3, and vasopressin 2 (V2) receptor were remarkably reduced as determined by qRT-PCR and/or Western blotting. Notably, inhibition of mitochondrial complex-1 by rotenone markedly reversed the downregulation of AQP1, AQP2, AQP3, and V2 In contrast, AQP4 was not affected by kidney obstruction or rotenone treatment. In a separate study, rotenone also attenuated AQPs' downregulation after 48-h UUO. To study the potential mechanisms in mediating the rotenone effects on AQPs, we examined the regulation of the COX-2/microsomal prostaglandin E synthase (mPGES)-1/PGE2/EP pathway and found that COX-2, mPGES-1, and renal PGE2 content were all significantly elevated in obstructive kidneys, which was not affected by rotenone treatment. For EP receptors, EP2 and EP4 but not EP1 and EP3 were upregulated in obstructive kidneys. Importantly, rotenone strikingly suppressed EP1 and EP4 but not EP2 and EP3 receptors. However, treatment of EP1 antagonist SC-51322 could not affect AQPs' reduction in obstructed kidneys. Collectively, these findings suggested an important role of mitochondrial dysfunction in modulating AQPs and V2 receptor in obstructive nephropathy possibly via prostaglandin-independent mechanisms.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP146032793	SC-51322		146032-79-3	Price

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