ArticleProceedings of the National Academy of Sciences of the United States of America2003
Chloride, not sodium, stimulates expression of the gamma subunit of Na/K-ATPase and activates JNK in response to hypertonicity in mouse IMCD3 cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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13 citing papers in PubMed, 33 citations in OpenAlex.
- Proton-activated chloride channel PACC1 as acid sensor in epidermal desquamation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Possible roles of CAHS proteins from Tardigrade in osmotic stress tolerance in mammalian cells.Cell structure and function · 2024Article
- ClAmerican journal of physiology. Cell physiology · 2020Review
- DeSUMOylation switches Kaiso from activator to repressor upon hyperosmotic stress.Cell death and differentiation · 2018Article
- Renal Mg handling, FXYD2 and the central role of the Na,K-ATPase.Physiological reports · 2018Review
- Hyperosmotic stress stimulates autophagy via polycystin-2.Oncotarget · 2017Article
- Deficiency of mPGES-1 exacerbates renal fibrosis and inflammation in mice with unilateral ureteral obstruction.American journal of physiology. Renal physiology · 2017Article
- Low-salt diet and cyclosporine nephrotoxicity: changes in kidney cell metabolism.Journal of proteome research · 2012Article
- FXYD proteins stabilize Na,K-ATPase: amplification of specific phosphatidylserine-protein interactions.The Journal of biological chemistry · 2011Article
- The hypertonic environment differentially regulates wild-type CFTR and TNR-CFTR chloride channels.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2010Article
- FXYD2 and Na,K-ATPase expression in isolated human proximal tubular cells: disturbed upregulation on renal hypomagnesemia?The Journal of membrane biology · 2009Article
- How do kidney cells adapt to survive in hypertonic inner medulla?Transactions of the American Clinical and Climatological Association · 2009Review
- Sodium chloride regulates Extracellular Regulated Kinase 1/2 in different tumor cell lines.Molecular and cellular biochemistry · 2006Article
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4 authors at 2 institutions in 1 country.
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Abstract
Hypertonicity induced by NaCl, but not by urea or mannitol, up-regulates expression of the gamma subunit of Na/K-ATPase in cells of the murine inner medullary collecting duct line (IMCD3) by activation of the Jun kinase 2 (JNK2) pathways. We examined the ionic mediators of the osmosensitive response. An increase in osmolality to 550 milliosmoles per kg of water (mosmol/kgH2O) for 48 h by replacement of NaCl with choline chloride did not prevent the up-regulation of the gamma subunit. Neither Na+ ionophores nor inhibitors of cellular Na+ uptake altered the up-regulation of the gamma subunit or JNK activation. Changes in cell cation concentrations driven by incubation in low-K+ medium were effective in up-regulating the alpha1 subunit of Na/K-ATPase but did not have any effect on the gamma subunit. The replacement of NaCl with choline chloride did not down-regulate gamma-subunit expression in cells adapted to hypertonicity. In contrast, the replacement of NaCl with sodium acetate, or pretreatment of cells with the Cl- channel inhibitor 5-nitro-2-(3-phenylpropyl-amino)benzoic acid (NPPB) completely blocked gamma-subunit up-regulation, inhibited JNK activation, and caused a significant decrement in cell survival in hypertonic but not isotonic conditions. In adapted cells, replacement of 300 mosmol/kgH2O NaCl with sodium acetate resulted in down-regulation of the gamma subunit. In conclusion, we describe a Na+-independent, Cl--dependent mechanism for hypertonicity-mediated activation of the JNK and the subsequent synthesis of the gamma subunit of Na/K-ATPase, which are necessary for cellular survival in these anisotonic conditions.
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