ArticleBritish journal of pharmacology2012
cAMP signalling protects proximal tubular epithelial cells from cisplatin-induced apoptosis via activation of Epac.
Article in British journal of pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 38 citations in OpenAlex.
- Epac1 Functions as a Central Cardioprotective cAMP Effector During Ischemic and β-adrenergic Preconditioning.Cardiovascular drugs and therapy · 2026Article
- Mechanistic study of the role of emodin in targeting and inhibiting the Rap1 signaling pathway to regulate epithelial-mesenchymal transition and reverse cisplatin resistance in hepatocellular carcinoma.Translational cancer research · 2026Article
- Multifaceted roles of Epac signaling in renal functions.The Biochemical journal · 2025Review
- Protocatechuic Acid Ameliorates Cisplatin-Induced Inflammation and Apoptosis in Mouse Proximal Tubular Cells.International journal of molecular sciences · 2025Article
- Article
- Calcitriol Reduces the Inflammation, Endothelial Damage and Oxidative Stress in AKI Caused by Cisplatin.International journal of molecular sciences · 2022Article
- Epac activation ameliorates tubulointerstitial inflammation in diabetic nephropathy.Acta pharmacologica Sinica · 2022Article
- Epac: A Promising Therapeutic Target for Vascular Diseases: A Review.Frontiers in pharmacology · 2022Review
- Review
- Review
- An increased cell cycle gene network determines MEK and Akt inhibitor double resistance in triple-negative breast cancer.Scientific reports · 2019Article
- Role of PI3K/Akt and MEK/ERK Signalling in cAMP/Epac-Mediated Endothelial Barrier Stabilisation.Frontiers in physiology · 2019Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Epac1 knockdown inhibits the proliferation of ovarian cancer cells by inactivating AKT/Cyclin D1/CDK4 pathway in vitro and in vivo.Medical oncology (Northwood, London, England) · 2016Article
- Hierarchical classification strategy for Phenotype extraction from epidermal growth factor receptor endocytosis screening.BMC bioinformatics · 2016Article
- Epac-Rap signaling reduces oxidative stress in the tubular epithelium.Journal of the American Society of Nephrology : JASN · 2014Article
- cAMP signaling prevents podocyte apoptosis via activation of protein kinase A and mitochondrial fusion.PloS one · 2014Article
- Role of guanine-nucleotide exchange factor Epac in renal physiology and pathophysiology.American journal of physiology. Renal physiology · 2013Review
- Multiple facets of cAMP signalling and physiological impact: cAMP compartmentalization in the lung.Pharmaceuticals (Basel, Switzerland) · 2012Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeNephrotoxicity is the principal dose-limiting factor for cisplatin chemotherapy and is primarily associated with proximal tubular epithelial cells, including disruption of cell adhesions and induction of apoptosis. Cell adhesion and survival is regulated by, amongst other factors, the small GTPase Rap and its activator, the exchange protein directly activated by cAMP (Epac). Epac is particularly enriched in renal tubule epithelium. This study investigates the cytoprotective effects of cAMP-Epac-Rap signalling in a model of cisplatin-induced renal cell injury. EXPERIMENTAL APPROACH: The Epac-selective cAMP analogue 8-pCPT-2'-O-Me-cAMP was used to activate the Epac-Rap signalling pathway in proximal tubular epithelial cells. Cells were exposed to cisplatin, in the presence or absence of 8-pCPT-2'-O-Me-cAMP, and nephrotoxicity was determined by monitoring cell-cell junctions and cell apoptosis. KEY
resultsActivation of Epac-Rap signalling preserves cell-cell junctions and protects against cell apoptosis of mouse proximal tubular cells during cisplatin treatment. Activation with the Epac-selective cAMP analogue 8-pCPT-2'-O-Me-cAMP or receptor-mediated induction of cAMP both induced cytoprotection against cisplatin, whereas a PKA-selective cAMP analogue was not cytoprotective. 8-pCPT-2'-O-Me-cAMP mediated cytoprotection was blocked by RNAi-mediated silencing of Epac-Rap signalling in these cells. In contrast, 8-pCPT-2'-O-Me-cAMP did not protect against cisplatin-induced cell death of cancer cells that lacked Epac1 expression. CONCLUSIONS AND IMPLICATIONS: Our study identifies activation of Epac-Rap signalling as a potential strategy for reducing the nephrotoxicity associated with cisplatin treatments and, as a result, broadens the therapeutic window of this chemotherapeutic agent.
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