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

TY - JOUR

T1 - Lack of cross-tolerance following heat and cadmium exposure in functional MDCK monolayers

AU - Dokladny, Karol

AU - Wharton, Walker

AU - Ma, Thomas Y

AU - Moseley, Pope L

PY - 2008/10

Y1 - 2008/10

N2 - 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.

AB - 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.

KW - Animals

KW - Cadmium Chloride/toxicity

KW - Cells, Cultured

KW - Dogs

KW - Electric Impedance

KW - Epithelial Cells/drug effects

KW - Gene Expression

KW - HSP70 Heat-Shock Proteins/metabolism

KW - Heat-Shock Response/drug effects

KW - Hot Temperature

KW - Kidney/drug effects

KW - Luciferases/metabolism

KW - Membrane Proteins/biosynthesis

KW - Occludin

U2 - 10.1002/jat.1352

DO - 10.1002/jat.1352

M3 - Journal article

C2 - 18418844

SN - 0260-437X

VL - 28

SP - 885

EP - 894

JO - Journal of Applied Toxicology

JF - Journal of Applied Toxicology

IS - 7

ER -