ArticleAmerican journal of physiology. Renal physiology2012
Hypotonic stress upregulates β- and γ-ENaC expression through suppression of ERK by inducing MKP-1.
Article in American journal of physiology. Renal physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 28 citations in OpenAlex.
- Trametinib-induced Hyponatremia in a Patient With Craniopharyngioma and Diabetes Insipidus.Journal of pediatric hematology/oncology · 2025Article
- KDM6A Demethylase Regulates Renal Sodium Excretion and Blood Pressure.Hypertension (Dallas, Tex. : 1979) · 2024Article
- Physiological roles of chloride ions in bodily and cellular functions.The journal of physiological sciences : JPS · 2023Review
- Submersion and hypoxia inhibit alveolar epithelial NaRespiratory research · 2023Article
- Aldosterone: Renal Action and Physiological Effects.Comprehensive Physiology · 2023Article
- A variant of ASIC2 mediates sodium retention in nephrotic syndrome.JCI insight · 2021Article
- Change in hydration indices associated with an increase in total water intake of more than 0.5 L/day, sustained over 4 weeks, in healthy young men with initial total water intake below 2 L/day.Physiological reports · 2017Article
- Hypotonic Stress-induced Down-regulation of Claudin-1 and -2 Mediated by Dephosphorylation and Clathrin-dependent Endocytosis in Renal Tubular Epithelial Cells.The Journal of biological chemistry · 2016Article
- How do kinases contribute to tonicity-dependent regulation of the transcription factor NFAT5?World journal of nephrology · 2016Review
- Potential Roles of Amiloride-Sensitive Sodium Channels in Cancer Development.BioMed research international · 2016Review
- Aldosterone modulates thiazide-sensitive sodium chloride cotransporter abundance via DUSP6-mediated ERK1/2 signaling pathway.American journal of physiology. Renal physiology · 2015Article
- Insulin is involved in transcriptional regulation of NKCC and the CFTR Cl(-) channel through PI3K activation and ERK inactivation in renal epithelial cells.The journal of physiological sciences : JPS · 2014Article
- ENaC activity and expression is decreased in the lungs of protein kinase C-α knockout mice.American journal of physiology. Lung cellular and molecular physiology · 2014Article
- Cytosolic chloride ion is a key factor in lysosomal acidification and function of autophagy in human gastric cancer cell.Journal of cellular and molecular medicine · 2014Article
- Low pH of interstitial fluid around hippocampus of the brain in diabetic OLETF rats.Molecular and cellular therapies · 2014Article
- Epoxyeicosatrienoic acids attenuating hypotonic-induced apoptosis of IMCD cells via γ-ENaC inhibition.PloS one · 2014Article
- Estradiol activates epithelial sodium channels in rat alveolar cells through the G protein-coupled estrogen receptor.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Cell-specific expression ofInternational journal of immunopathology and pharmacologyArticle
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4 authors at 3 institutions in 2 countries.
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Abstract
We investigated a physiological role for ERK, a member of the MAPK family, in the hypotonic stimulation of epithelial Na(+) channel (ENaC)-mediated Na(+) reabsorption in renal epithelial A6 cells. We show that hypotonic stress causes a major dephosphorylation of ERK following a rapid transient phosphorylation. PD98059 (a MEK inhibitor) increases dephosphorylated ERK and enhances the hypotonic-stress-stimulated Na(+) reabsorption. ERK dephosphorylation is mediated by MAPK phosphatase (MKP). Hypotonic stress activates p38, which in turn induces MKP-1 and to a lesser extent MKP-3 mRNA expression. Inhibition of p38 suppresses MKP-1 induction, preventing hypotonic stress from dephosphorylating ERK. Inhibition of MKP-1 and -3 by the inhibitor NSC95397 also suppresses the hypotonicity-induced dephosphorylation of ERK. NSC95397 reduces both β- and γ-ENaC mRNA expression and ENaC-mediated Na(+) reabsorption stimulated by hypotonic stress. In contrast, pretreatment with PD98059 significantly enhances mRNA and protein expression of β- and γ-ENaC even under isotonic conditions. However, PD98059 only stimulates Na(+) reabsorption in response to hypotonic stress, suggesting that ERK inactivation by itself (i.e., under isotonic conditions) is not sufficient to stimulate Na(+) reabsorption, even though ERK inactivation enhances β- and γ-ENaC expression. Based on these results, we conclude that hypotonic stress stimulates Na(+) reabsorption through at least two signaling pathways: 1) induction of MKP-1 that suppresses ERK activity and induces β- and γ-ENaC expression, and 2) promotion of translocation of the newly synthesized ENaC to the apical membrane.
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