ArticleJournal of the American Society of Nephrology : JASN2014
Epac-Rap signaling reduces oxidative stress in the tubular epithelium.
Article in Journal of the American Society of Nephrology : JASN, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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The trial behind it
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Thioredoxin interacting protein (TXNIP), a redox regulator, mediates the EPAC-RAP1 signaling dependency of primary melanoma.Oncogene · 2026Article
- Multifaceted roles of Epac signaling in renal functions.The Biochemical journal · 2025Review
- Transcriptomics reveals dynamic changes in the "gene profiles" of rat supraspinatus tendon at three different time points after diabetes induction.BMC medical genomics · 2024Article
- Celastrol Ameliorates Neuronal Mitochondrial Dysfunction Induced by Intracerebral Hemorrhage via Targeting cAMP-Activated Exchange Protein-1.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Effect ofInternational journal of molecular sciences · 2024Article
- The old second messenger cAMP teams up with novel cell death mechanisms: potential translational therapeutical benefit for Alzheimer's disease and Parkinson's disease.Frontiers in physiology · 2023Review
- EPAC Regulates Melanoma Growth by Stimulating mTORC1 Signaling and Loss of EPAC Signaling Dependence Correlates with Melanoma Progression.Molecular cancer research : MCR · 2022Article
- Puerarin attenuates diabetic kidney injury through interaction with Guanidine nucleotide-binding protein Gi subunit alpha-1 (Gnai1) subunit.Journal of cellular and molecular medicine · 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
- Epac1 and PKA agonists inhibit ROS to reduce NLRP3 inflammasome proteins in retinal endothelial cells.Molecular vision · 2022Article
- Review
- The Role of Epac in Cancer Progression.International journal of molecular sciences · 2020Review
- Angiotensin-(1-7) Attenuates Protein O-GlcNAcylation in the Retina by EPAC/Rap1-Dependent Inhibition of O-GlcNAc Transferase.Investigative ophthalmology & visual science · 2020Article
- Stimulation of GLP-1 Receptor Inhibits Methylglyoxal-Induced Mitochondrial Dysfunctions in H9c2 Cardiomyoblasts: Potential Role of Epac/PI3K/Akt Pathway.Frontiers in pharmacology · 2020Article
- A peek into Epac physiology in the kidney.American journal of physiology. Renal physiology · 2019Article
- Selective small-molecule EPAC activators.Biochemical Society transactions · 2019Review
- Antiproliferative activities of the second-generation antipsychotic drug sertindole against breast cancers with a potential application for treatment of breast-to-brain metastases.Scientific reports · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- C-X-C Chemokine Receptor Type 4 Plays a Crucial Role in Mediating Oxidative Stress-Induced Podocyte Injury.Antioxidants & redox signaling · 2017Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of Rap1 by exchange protein activated by cAMP (Epac) promotes cell adhesion and actin cytoskeletal polarization. Pharmacologic activation of Epac-Rap signaling by the Epac-selective cAMP analog 8-pCPT-2'-O-Me-cAMP during ischemia-reperfusion (IR) injury reduces renal failure and application of 8-pCPT-2'-O-Me-cAMP promotes renal cell survival during exposure to the nephrotoxicant cisplatin. Here, we found that activation of Epac by 8-pCPT-2'-O-Me-cAMP reduced production of reactive oxygen species during reoxygenation after hypoxia by decreasing mitochondrial superoxide production. Epac activation prevented disruption of tubular morphology during diethyl maleate-induced oxidative stress in an organotypic three-dimensional culture assay. In vivo renal targeting of 8-pCPT-2'-O-Me-cAMP to proximal tubules using a kidney-selective drug carrier approach resulted in prolonged activation of Rap1 compared with nonconjugated 8-pCPT-2'-O-Me-cAMP. Activation of Epac reduced antioxidant signaling during IR injury and prevented tubular epithelial injury, apoptosis, and renal failure. Our data suggest that Epac1 decreases reactive oxygen species production by preventing mitochondrial superoxide formation during IR injury, thus limiting the degree of oxidative stress. These findings indicate a new role for activation of Epac as a therapeutic application in renal injury associated with oxidative stress.
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Registered trials
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.