Expression of heat shock protein 60 in human proximal tubule cells exposed to heat, sodium arsenite and CdCl2

The expression of hsp 60 mRNA and protein were determined in human proximal tubule cells (WPT) exposed to lethal and sub-lethal concentrations of Cd2+ under both acute and extended conditions of exposure. It was demonstrated that HPT cells exhibited the classic heat shock response when subjected to a physical (heat) or chemical stress (sodium arsenite). Neat stress, elevated temperature at 42.5 degrees C for 1 h. caused an increase in both hsp 60 mRNA and protein following removal of the stress. Similar results were obtained when the cells were subjected to a classic chemical stress of exposure to 100 mu M sodimn arsenite for 4 h. Acute exposure of HPT cells to 53.4 mu M CdCl2 for 4 h also resulted in an increase in hsp 60 mRNA and protein following removal of the metal. An extended exposure to Cd2+ was modeled by treating the cells continuously with Cd2+ at both lethal and sub-lethal levels over a 16-day time course. It was demonstrated that chronic exposure to Cd2+ failed to increase either hsp 60 mRNA or protein expression in HPT cells, even at concentrations of Cd2+ that were lethal to the cells during the time course. In fact, hsp 60 protein levels were decreased compared to controls at lethal levels of Cd2+ exposure. These findings suggest that hsp 60 expression may have two distinct roles when the human proximal tubule cell is exposed to Cd2+. A protective role through hsp 60 induction when the proximal tubule cell is acutely exposed to Cd2+ and a deleterious role when hsp 60 protein is down-regulated during extended exposure to Cd2+. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.