How Aldosterone Keeps Salt In The Body

Main Category: Urology / Nephrology
Also Included In: Endocrinology;  Hypertension;  Cardiovascular / Cardiology
Article Date: 07 Mar 2007 - 9:00 PDT

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The hormone aldosterone regulates the amount of sodium (Na+) that we retain in our body and how much excrete in our urine by activating epithelial Na+ channels (ENaCs). In this way it has a major influence on blood pressure and extracellular fluid volume, thereby influencing the course of cardiovascular and renal diseases. Although it is known that aldosterone induces the expression of a protein known as SGK1 and that SGK1 can increase the expression of the alpha-subunit of ENaC (ENaC-alpha), the precise molecular details of this pathway have not been clearly determined.

In a study appearing in the March issue of the Journal of Clinical Investigation, Bruce Kone and colleagues from the University of Texas Medical School at Houston, demonstrate that in the mouse, SGK1 increases the expression of ENaC-alpha by phosphorylating a protein known as AF9. Unphosphorylated AF9 can bind a protein known as Dot1a and this complex sits on the promoter of the gene that encodes ENaC-alpha, by preventing histone methylation and thereby preventing the gene from being expressed. Upon phosphorylation by SGK1, the AF9-Dot1A complex breaks part, enabling high levels of the gene encoding ENaC-alpha to be expressed. This study therefore identifies the molecular pathway by which aldosterone activates ENaCs in the mouse and is likely to apply to other genes encoding proteins activated by aldosterone.

In an accompanying commentary, David Pearce and Thomas Kleyman clarify the importance of this study for our understanding of sodium retention and outline the questions that remain to be answered before this increased understanding can be translated to the development of drugs for the treatment of high blood pressure.

TITLE: Aldosterone-induced Sgk1 relieves Dot1a-Af9-mediated transcriptional repression of epithelial Na+ channel-alpha

AUTHOR CONTACT:

Bruce C. Kone
University of Texas Medical School at Houston, Houston, Texas, USA.

Wenzheng Zhang
University of Texas Medical School at Houston, Houston, Texas, USA.

TITLE: Salt, sodium channels, and SGK1

AUTHOR CONTACT:
Thomas R. Kleyman
University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

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JCI table of contents -- March 1, 2007

Contact: Karen Honey
Journal of Clinical Investigation

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