Na+–H+ exchanger-1 (NHE1) regulation in kidney proximal tubule

Abstract

The ubiquitously expressed plasma membrane Na+–H+ exchanger NHE1 is a 12 transmembrane-spanning protein that directs important cell functions such as homeostatic intracellular volume and pH control. The 315 amino acid cytosolic tail of NHE1 binds plasma membrane phospholipids and multiple proteins that regulate additional, ion-translocation independent functions. This review focuses on NHE1 structure/function relationships, as well as the role of NHE1 in kidney proximal tubule functions, including pH regulation, vectorial Na+ transport, cell volume control and cell survival. The implications of these functions are particularly critical in the setting of progressive, albuminuric kidney diseases, where the accumulation of reabsorbed fatty acids leads to disruption of NHE1-membrane phospholipid interactions and tubular atrophy, which is a poor prognostic factor for progression to end stage renal disease. This review amplifies the vital role of the proximal tubule NHE1 Na+–H+ exchanger as a kidney cell survival factor.

Proximal Tubulopathy: Prime Mover and Key Therapeutic Target in Diabetic Kidney Disease

“…In addition to the hypoxia, several other nonhypoxiarelated proximal tubule pathways involved in the development of diabetic kidney disease have been the subjects of recent reviews. These include the now well-documented local, predominantly proximal tubule-based renin-angiotensin system (74), the toxic effects of albumin bound fatty acids (75,76), and the activation of epidermal growth factor receptor signaling pathways (77). Still more recently, and not yet the subject of detailed review, is the exploration whereby diabetic kidney disease, like most forms of CKD, once started, continues to progress inexorably.…”

What Is the Impact of Diet on Nutritional Diarrhea Associated with Gut Microbiota in Weaning Piglets: A System Review

“…In the intestine, NHE1 (SLC9A1), NHE2 (SLC9A2), NHE3 (SLC9A3), and NHE8 (SLC9A8) have been shown to be present in the intestinal epithelium [105,107]. NHE1 (SLC9A1) is expressed in the basolateral membrane of the intestinal epithelial cells, is not affected by Na + depletion, and does not contribute to luminal ion and water absorption [108,109]. NHE2 (SLC9A2) and NHE3 (SLC9A3) are both expressed in the intestinal epithelium, with a larger contribution of NHE3 (SLC9A3) to Na + absorption under control conditions [110].…”

AMP-Activated Protein Kinase (AMPK)-Dependent Regulation of Renal Transport

“…The ubiquitous Na + /H + exchanger isoform 1 (NHE1) participates in cell volume and pH regulation by extruding one cytosolic H + in exchange for one extracellular Na + [ 136 , 137 ]. NHE1 is expressed in all parts of the nephron, including the proximal tubule.…”