Direct Control of Na+-K+-2Cl−-Cotransport Protein (NKCC1) Expression with Aldosterone
Document Type
Article
Publication Date
2014
Keywords
NKCC1, Na+-K+-2Cl−-cotransport protein, pathway regulation, steroid hormone, aging, physiological systems, therapeutics
Digital Object Identifier (DOI)
https://doi.org/10.1152/ajpcell.00096.2013
Abstract
Sodium/potassium/chloride cotransporter (NKCC1) proteins play important roles in Na+ and K+ concentrations in key physiological systems, including cardiac, vascular, renal, nervous, and sensory systems. NKCC1 levels and functionality are altered in certain disease states, and tend to decline with age. A sensitive, effective way of regulating NKCC1 protein expression has significant biotherapeutic possibilities. The purpose of the present investigation was to determine if the naturally occurring hormone aldosterone (ALD) could regulate NKCC1 protein expression. Application of ALD to a human cell line (HT-29) revealed that ALD can regulate NKCC1 protein expression, quite sensitively and rapidly, independent of mRNA expression changes. Utilization of a specific inhibitor of mineralocorticoid receptors, eplerenone, implicated these receptors as part of the ALD mechanism of action. Further experiments with cycloheximide (protein synthesis inhibitor) and MG132 (proteasome inhibitor) revealed that ALD can upregulate NKCC1 by increasing protein stability, i.e., reducing ubiquitination of NKCC1. Having a procedure for controlling NKCC1 protein expression opens the doors for therapeutic interventions for diseases involving the mis-regulation or depletion of NKCC1 proteins, for example during aging.
Was this content written or created while at USF?
Yes
Citation / Publisher Attribution
American Journal of Physiology-Cell Physiology, v. 306, issue 1, p. C66-C675
Scholar Commons Citation
Ding, Bo; Frisina, Robert D.; Zhu, Xiaoxia; Sakai, Yoshihisa; Sokolowski, Bernd; and Walton, Joseph P., "Direct Control of Na+-K+-2Cl−-Cotransport Protein (NKCC1) Expression with Aldosterone" (2014). Communication Sciences and Disorders Faculty Publications. 24.
https://digitalcommons.usf.edu/csd_facpub/24
