Details

Autor(en) / Beteiligte

• Alaynick, William A
• Way, James M
• Wilson, Stephanie A
• Benson, William G
• Pei, Liming
• Downes, Michael
• Yu, Ruth
• Jonker, Johan W
• Holt, Jason A
• Rajpal, Deepak K
• Li, Hao
• Stuart, Joan
• McPherson, Ruth
• Remlinger, Katja S
• Chang, Ching-Yi
• McDonnell, Donald P
• Evans, Ronald M
• Billin, Andrew N

Titel

ERRγ Regulates Cardiac, Gastric, and Renal Potassium Homeostasis

Ist Teil von

• Molecular endocrinology (Baltimore, Md.), 2010-02, Vol.24 (2), p.299-309

Ort / Verlag

Endocrine Society

Erscheinungsjahr

2010

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• Energy production by oxidative metabolism in kidney, stomach, and heart, is primarily expended in establishing ion gradients to drive renal electrolyte homeostasis, gastric acid secretion, and cardiac muscle contraction, respectively. In addition to orchestrating transcriptional control of oxidative metabolism, the orphan nuclear receptor, estrogen-related receptor γ (ERRγ), coordinates expression of genes central to ion homeostasis in oxidative tissues. Renal, gastric, and cardiac tissues subjected to genomic analysis of expression in perinatal ERRγ null mice revealed a characteristic dysregulation of genes involved in transport processes, exemplified by the voltage-gated potassium channel, Kcne2. Consistently, ERRγ null animals die during the first 72 h of life with elevated serum potassium, reductions in key gastric acid production markers, and cardiac arrhythmia with prolonged QT intervals. In addition, we find altered expression of several genes associated with hypertension in ERRγ null mice. These findings suggest a potential role for genetic polymorphisms at the ERRγ locus and ERRγ modulators in the etiology and treatment of renal, gastric, and cardiac dysfunction. In addition to regulation of oxidative metabolism, ERRγ regulates ion homeostasis, especially potassium, in renal, gastric and cardiac tissues and appears to influence hypertension in mouse and human.