ArticleMolecular vision2010
Elevated cAMP opposes (TNF-alpha)-induced loss in the barrier integrity of corneal endothelium.
Article in Molecular vision, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 22 citations in OpenAlex.
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- The sleep quality- and myopia-linked PDE11A-Y727C variant impacts neural physiology by reducing catalytic activity and altering subcellular compartmentalization of the enzyme.bioRxiv : the preprint server for biology · 2023Article
- Effects of ROCK Inhibitors on Apoptosis of Corneal Endothelial Cells in CMV-Positive Posner-Schlossman Syndrome Patients.Investigative ophthalmology & visual science · 2020Article
- Adipokines and Obesity. Potential Link to Metabolic Disorders and Chronic Complications.International journal of molecular sciences · 2020Review
- Article
- Rap1 GTPase activation and barrier enhancement in rpe inhibits choroidal neovascularization in vivo.PloS one · 2013Article
- Cell signaling in regulation of the barrier integrity of the corneal endothelium.Experimental eye research · 2012Review
- Barrier stabilizing mediators in regulation of microvascular endothelial permeability.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2012Review
- The immunomodulatory effects of rolipram abolish drug-resistant latent phase ofJournal of microscopy and ultrastructureArticle
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
purposeElevated cyclic adenosine monophosphate (cAMP) enhances the barrier integrity of the corneal endothelium and thereby facilitates stromal hydration control, which is necessary for corneal transparency. This study investigates whether elevated cAMP is effective against the tumor necrosis factor-alpha (TNF-alpha)-induced loss of barrier integrity in monolayers of bovine corneal endothelial cells (BCEC).
methodsBCEC in primary culture were used for the study. Trans-endothelial electrical resistance (TER), a measure of barrier integrity, was determined by electrical cell-substrate impedance sensing. The changes were also ascertained by measuring paracellular permeability to fluorescein isothiocyanate (FITC)-dextran (10 kDa) across cells grown on porous culture inserts, and by immunofluorescence imaging of the apical junctional complex (AJC). The activation of p38 MAP kinase was assessed using western blotting.
resultsCo-treatment with forskolin, which activates adenylate cyclase, and rolipram, which inhibits cAMP-dependent phosphodiesterase PDE4, reduced the TNF-alpha-induced increase in the flux of FITC-dextran. Similar co-treatment also prevented the TNF-alpha-induced disorganization of zona occludens-1 (ZO-1) and cadherins at the AJC. Co-treatment, as well pre-treatment, with forskolin plus rolipram prevented the TNF-alpha-induced decrease in TER. The influence of the agents was significant after 12 h of exposure to the cytokine. This effect was also mimicked by A2B agonists, adenosine and 5'-N-ethylcarboxamidoadenosine (NECA), which are known to mobilize cAMP in BCEC. Elevated cAMP also inhibited the cytokine-induced activation of p38 MAP kinase, and further blocked the disassembly of microtubules as well as the disruption of the PAMR (peri-junctional actomyosin ring) at the AJC.
conclusionsThese results suggest that elevated cAMP opposes the TNF-alpha-induced loss in barrier integrity of the corneal endothelium. This effect follows inhibition of the cytokine-induced activation of p38 MAP kinase and its downstream signaling involved in the disruption of AJC and PAMR, as well as the disassembly of microtubules.
Indexed as
Identifiers
20824160PMC2932488W1549103838What OpenQuestion holds
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.