Deciphering the mechanisms of the Na+/H+ exchanger-3 regulation in organ dysfunction

The Na(+)/H(+) exchanger-3 (NHE3) belongs to the mammalian NHE protein family and catalyzes the electro-neutral exchange of extracellular sodium for intracellular proton across cellular membranes. Its transport function is of essential importance for the maintenance of the body's salt and water...

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Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2012-06, Vol.302 (11), p.C1569-C1587
Main Authors: Girardi, Adriana C C, Di Sole, Francesca
Format: Article
Language:English
Subjects:
Acid-Base Equilibrium
Acute Kidney Injury - pathology
Animals
Biological Transport, Active - physiology
Catalysis
Cellular biology
Diabetic Nephropathies - metabolism
Diabetic Nephropathies - pathology
Diarrhea - metabolism
Diarrhea - pathology
Heart Failure - metabolism
Heart Failure - pathology
Humans
Hypertension - metabolism
Hypertension - pathology
Ion Transport - physiology
Kidney Diseases - metabolism
Kidney Diseases - pathology
Medical disorders
Membranes
Physiology
Proteins
Sodium - metabolism
Sodium-Hydrogen Exchanger 3
Sodium-Hydrogen Exchangers - metabolism
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Summary:The Na(+)/H(+) exchanger-3 (NHE3) belongs to the mammalian NHE protein family and catalyzes the electro-neutral exchange of extracellular sodium for intracellular proton across cellular membranes. Its transport function is of essential importance for the maintenance of the body's salt and water homeostasis as well as acid-base balance. Indeed, NHE3 activity is finely regulated by a variety of stimuli, both acutely and chronically, and its transport function is fundamental for a multiplicity of severe and world-wide infection-pathological conditions. This review aims to provide a concise overview of NHE3 physiology and discusses the role of NHE3 in clinical conditions of prominent importance, specifically in hypertension, diabetic nephropathy, heart failure, acute kidney injury, and diarrhea. Study of NHE3 function in models of these diseases has contributed to the deciphering of mechanisms that control the delicate ion balance disrupted in these disorders. The majority of the findings indicate that NHE3 transport function is activated before the onset of hypertension and inhibited thereafter; NHE3 transport function is also upregulated in diabetic nephropathy and heart failure, while it is reported to be downregulated in acute kidney injury and in diarrhea. The molecular mechanisms activated during these pathological conditions to regulate NHE3 transport function are examined with the aim of linking NHE3 dysfunction to the analyzed clinical disorders.
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.00017.2012