Oxidized alkyl phospholipids stimulate sodium transport in proximal tubules via a nongenomic PPARγ-dependent pathway

Abstract

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Oxidative-stress-responsive kinase 1 is the master regulator of proximal tubular sodium transport

“…We previously reported that PPARγ agonists enhance PT Na transport via ERK-mediated non-genomic effects 10,11 . We found that pioglitazone (PGZ), a PPARγ agonist, stimulated NHE and NBCe1 activity in rat PTs.…”

“…PTs were isolated as previously described [9][10][11][12] . PT was isolated from human and rat kidney cortex.…”

“…The luminally collapsed PT was incubated with an acetoxymethyl ester form of a pH-sensitive uorescent dye 2',7'-bis(carboxyethyl)- Corporation, Osaka, Japan) at 300 nM. All of them exhibited su cient inhibitory activities without affecting the basal NBCe1 activity in PTs [9][10][11][12]20 . NBCe1 activity was calculated using the rate of pHi decrease in response to bath HCO 3 reduction and the buffer capacity.…”

“…Luminal NHE activity was determined as previously described 10,11,43,44 . Brie y, the PT (S2 segment)…”

“…Na transport in the PT is primarily regulated by the coordinated action of the Na-H exchange transporter (NHE)3 and the Na-HCO 3 cotransporter (NBCe1) expressed on the luminal and basement membrane sides, respectively 8 . We previously revealed the following regulatory mechanisms of NBCe1 and NHE3 in the PT: i) insulin stimulates NBCe1 via insulin receptor substrate (IRS)2/Akt2 9 , ii) peroxisome proliferator-activated receptor gamma (PPARγ) agonists regulate NHE3 and NBCe1 via extracellular signal-regulated kinases (ERK) 10,11 , and iii) angiotensin II (AngII) regulates NHE3 and NBCe1 via ERK 12 . These results strongly suggest the presence of master regulators of Na transport in the PT, although the details remain unclear.…”