title: Cortisol regulates epithelial permeability and sodium losses in zebrafish exposed to acidic water.
abstract: The effects of cortisol on epithelial permeability and sodium (Na(+)) handling during acid exposure were investigated in larval zebrafish (Danio rerio). The results demonstrated that the whole-body absorption of the paracellular permeability marker polyethylene glycol-4000 (PEG-4000) decreased with increasing levels of exogenous cortisol. Western blot analysis revealed that the abundance of the epithelial tight junction proteins occludin-a and claudin-b was increased after cortisol treatment. Furthermore, translational gene knockdown of claudin-b using an antisense morpholino oligonucleotide caused an increase in the permeability to PEG-4000, which was mitigated by cortisol treatment, further suggesting a role for cortisol in reducing paracellular permeability. Exposure to acidic water (pH 4.0 vs 7.6) caused an expected increase in the diffusive loss of Na(+) and a decrease in whole-body Na(+) levels. These disruptive effects of acute acid exposure on Na(+) balance were reduced by treatment of larvae with exogenous cortisol. Translational knockdown of the glucocorticoid receptor (GR) abolished the effects of cortisol on epithelial PEG permeability, suggesting that activation of GR was probably the major signaling pathway for reducing epithelial permeability. During acid exposure, the epithelial PEG permeability in the GR morphants was significantly higher than in the control fish. Additionally, GR morphants exhibited a more pronounced diffusive loss of Na(+) than the control fish during acid exposure. These findings suggest that cortisol may help to minimize the negative consequences of acid exposure on Na(+) homoeostasis via GR-mediated reductions in epithelial permeability and paracellular Na(+) loss.
authors.affiliation: Department of Biology, University of Ottawa, 30 Marie Curie, Ottawa, Ontario, Canada K1N 6N5. wkwong@uottawa.ca
authors.forename: Raymond W M
authors.initials: RW
authors.lastname: Kwong
authors.forename: Steve F
authors.initials: SF
authors.lastname: Perry
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D057167:Claudins / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006854:Hydrocortisone / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D010539:Permeability / Q000187:drug effects; D012964:Sodium / Q000378:metabolism*; D019108:Tight Junctions / Q000187:drug effects / Q000378:metabolism*; D014867:Water; D015027:Zebrafish
chemical_list: D057167:Claudins; D014867:Water; D012964:Sodium; D006854:Hydrocortisone