ArticleThe Journal of pharmacology and experimental therapeutics2008
The protein kinase A pathway contributes to Hg2+-induced alterations in phosphorylation and subcellular distribution of occludin associated with increased tight junction permeability of salivary epithelial cell monolayers.
Article in The Journal of pharmacology and experimental therapeutics, 2008. 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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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Vascular Endothelial Barrier in Salivary Glands: From Physiological Regulation to Pathological Impairment of Secretion.International journal of molecular sciences · 2026Review
- Keratinocytes regulate intraepithelial lymphocytes homing and mediate mucosal barrier integrity via JAK2/STAT3 signaling in oral lichen planus.Frontiers in immunology · 2026Article
- Snow White's tale in nephrology: the emerging threat of skin-whitening creams on kidney health.Clinical kidney journal · 2025Review
- Simple graphical approach to investigate differences in transepithelial paracellular leak pathway permeability.Physiological reports · 2022Article
- Uremic Toxic Blood-Brain Barrier Disruption Mediated by AhR Activation Leads to Cognitive Impairment during Experimental Renal Dysfunction.Journal of the American Society of Nephrology : JASN · 2020Article
- CaJournal of molecular histology · 2018Article
- Toxicodynamics of Lead, Cadmium, Mercury and Arsenic- induced kidney toxicity and treatment strategy: A mini review.Toxicology reports · 2018Review
- TRPV1 in Salivary Gland Epithelial Cells Is Not Involved in Salivary Secretion via Transcellular Pathway.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2014Article
- Bile duct epithelial tight junctions and barrier function.Tissue barriers · 2013Review
- The role of aquaporin and tight junction proteins in the regulation of water movement in larval zebrafish (Danio rerio).PloS one · 2013Article
- Tight junction proteins and oxidative stress in heavy metals-induced nephrotoxicity.BioMed research international · 2013Review
- Adiponectin increases secretion of rat submandibular gland via adiponectin receptors-mediated AMPK signaling.PloS one · 2013Article
- Occludin: one protein, many forms.Molecular and cellular biology · 2012Review
- Functional characterization of water transport and cellular localization of three aquaporin paralogs in the salmonid intestine.Frontiers in physiology · 2011Article
- Inflammatory mediators weaken the amniotic membrane barrier through disruption of tight junctions.The Journal of physiology · 2010Article
- Nitric oxide and airway epithelial barrier function: regulation of tight junction proteins and epithelial permeability.Archives of biochemistry and biophysics · 2009Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Hg(2+) is commonly used as an inhibitor of many aquaporins during measurements of transcellular water transport. To investigate whether it could also act on the paracellular water transport pathway, we asked whether addition of Hg(2+) affected transport of radiolabeled probes through tight junctions of a salivary epithelial cell monolayer. Inclusion of 1 mM Hg(2+) decreased transepithelial electrical resistance by 8-fold and augmented mannitol and raffinose flux by 13-fold, which translated into an estimated 44% increase in pore radius at the tight junction. These Hg(2+)-induced effects could be partially blocked by the protein kinase A (PKA) inhibitor N-[2-((p-bromocinnamyl) amino) ethyl]-5-isoquinolinesulfonamide, 2HCl (H89), suggesting that both-PKA dependent and PKA-independent mechanisms contribute to tight junction regulation. Western blot analyses showed a 2-fold decrease in tight junction-associated occludin after Hg(2+) treatment and the presence of a novel hyperphosphorylated form of occludin in the cytoplasmic fraction. These findings were corroborated by confocal imaging. The results from this study reveal a novel contribution of the PKA pathway in Hg(2+)-induced regulation of tight junction permeability in the salivary epithelial barrier. Therapeutically, this could be explored for pharmacological intervention in the treatment of dry mouth, Sjögren's syndrome, and possibly other disorders of fluid transport.
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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.