Lack of cross-tolerance following heat and cadmium exposure in functional MDCK monolayers

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Exposure of monolayers of Madin-Darby canine kidney epithelial (MDCK) cells to a mild heat stimulus induces a state of physiological thermotolerance in which epithelial barrier function is maintained following a second more severe heat stress. We have previously shown that expression of exogenous HSP70 fully mimics the effects of the conditioning heat stress. Exposure of MDCK cells to elevated temperatures or medium containing CdCl2 caused a robust increase in cellular levels of HSP70. Pretreatment of MDCK monolayers with cadmium but not heat caused a small protection of epithelial barrier function against a second challenge with cadmium. In addition, a prior exposure of monolayers to cadmium at levels sufficient to induce HSP70 expression and increased cellular chaperone activity did not afford protection against a subsequent thermal challenge. Therefore multiple stress-specific cellular pathways impinge on the ability of heat shock proteins to induce physiological thermotolerance. Occludin, a component of tight junctions, is induced in MDCK cells engineered to express high levels of exogenous HSP70, potentially accounting for an elevation in baseline resistance. However neither basal levels of occludin, nor alterations in occludin expression, were correlated with epithelial barrier function in MDCK cells either exposed to elevated temperatures or challenged with cadmium.

Original languageEnglish
JournalJournal of Applied Toxicology
Volume28
Issue number7
Pages (from-to)885-94
Number of pages10
ISSN0260-437X
DOIs
Publication statusPublished - Oct 2008

    Research areas

  • Animals, Cadmium Chloride/toxicity, Cells, Cultured, Dogs, Electric Impedance, Epithelial Cells/drug effects, Gene Expression, HSP70 Heat-Shock Proteins/metabolism, Heat-Shock Response/drug effects, Hot Temperature, Kidney/drug effects, Luciferases/metabolism, Membrane Proteins/biosynthesis, Occludin

ID: 202297045