ArticleJournal of the American Society of Nephrology : JASN2011
AMPK potentiates hypertonicity-induced apoptosis by suppressing NFκB/COX-2 in medullary interstitial cells.
Article in Journal of the American Society of Nephrology : JASN, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 29 citations in OpenAlex.
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- The NF-κB/FXR/TonEBP pathway protects renal medullary interstitial cells against hypertonic stress.Journal of cellular and molecular medicine · 2024Article
- Neutral amino acid transporter SLC38A2 protects renal medulla from hyperosmolarity-induced ferroptosis.eLife · 2023Article
- The Role of Peroxisome Proliferator-Activated Receptors in Kidney Diseases.Frontiers in pharmacology · 2022Review
- NFAT5-Mediated Signalling Pathways in Viral Infection and Cardiovascular Dysfunction.International journal of molecular sciences · 2021Review
- The interaction between protein kinase A and progesterone on basal and inflammation-induced myometrial oxytocin receptor expression.PloS one · 2020Article
- Role of PKC and AMPK in hypertonicity-stimulated water reabsorption in rat inner medullary collecting ducts.American journal of physiology. Renal physiology · 2019Article
- Farnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Involvement of AMP-activated Protein Kinase (AMPK) in Regulation of Cell Membrane Potential in a Gastric Cancer Cell Line.Scientific reports · 2018Article
- NF-κB-dependent upregulation of (pro)renin receptor mediates high-NaCl-induced apoptosis in mouse inner medullary collecting duct cells.American journal of physiology. Cell physiology · 2017Article
- Glucose-dependent regulation of pregnane X receptor is modulated by AMP-activated protein kinase.Scientific reports · 2017Article
- How do kinases contribute to tonicity-dependent regulation of the transcription factor NFAT5?World journal of nephrology · 2016Review
- Regulation of ion channels and transporters by AMP-activated kinase (AMPK).Channels (Austin, Tex.) · 2014Review
- Long-term cultured mesenchymal stem cells frequently develop genomic mutations but do not undergo malignant transformation.Cell death & disease · 2013Article
- High NaCl-induced inhibition of PTG contributes to activation of NFAT5 through attenuation of the negative effect of SHP-1.American journal of physiology. Renal physiology · 2013Article
- The outcome of renal ischemia-reperfusion injury is unchanged in AMPK-β1 deficient mice.PloS one · 2012Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cells residing in the hypertonic, hypoxic renal medulla depend on dynamic adaptation mechanisms to respond to changes in energy supply and demand. The serine/threonine kinase 5'-AMP protein kinase (AMPK) is a sensor of cellular energy status, but whether it contributes to the survival of cells in the renal medulla is unknown. Here, hypertonic conditions induced a decrease in AMPK phosphorylation within 12 hours in renal medullary interstitial cells (RMIC), followed by a gradual return to baseline levels. Activation of AMPK markedly increased hypertonicity-induced apoptosis of RMICs and suppressed both hypertonicity-induced NFκB nuclear translocation and cyclooxygenase-2 (COX-2) activation; overexpression of COX-2 significantly attenuated these effects. AMPK activation also markedly reduced generation of reactive oxygen species and nuclear expression of tonicity-responsive enhancer-binding protein, which prevented upregulation of osmoprotective genes. In vivo, pharmacologic activation of AMPK led to massive apoptosis of RMICs and renal dysfunction in the setting of water deprivation in mice. Taken together, these results identify a critical role for AMPK in the maintenance of RMIC viability and suggest that AMPK modulates the NFκB-COX-2 survival pathway in the renal medulla. Furthermore, this study raises safety concerns for the development of AMPK activators as anti-diabetic drugs, especially for patients prone to dehydration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.