Expression of hsp 27, hsp 60, hsc 70, and hsp 70 by immortalized human proximal tubule cells (HK-2) following exposure to heat shock, sodium arsenite, or cadmium chloride

The expression of hsp 27, hsp 60, hsc 70, and hsp 70 mRNA and protein was d etermined in immortalized human proximal tubule cells ( HK-2) exposed to he at shock, sodium arsenite, or cadmium chloride (CdCl2) under both acute and extended conditions of exposure. It was demonstrated that the HK-2 cells d id not exhibit the classic heat-shock response when subjected to an acute p hysical ( heat) or chemical stress ( sodium arsenite or CdCl2). Heat stress , elevated temperature at 42.5 degreesC for 1 h, caused a marked increase o nly in hsp 70 mRNA and protein, but not hsp 27 or hsp 60 mRNA and protein. Similar results were obtained when the cells were subjected to a classic ch emical stress of exposure to 100 muM sodium arsenite for 4 h or CdCl2 for 4 h. These findings were in contrast to those found previously with mortal h uman proximal tubule ( HPT) cells, where acute stress by all three stimuli elicited marked increases in hsp 27, hsp 60, and hsp 70 mRNA and protein. I t was shown that the basal levels of expression of hsp 27 and hsp 60 in the HK-2 cells were elevated when compared to those found in unstressed HPT ce lls and that the basal levels were similar to those found in HPT cells unde r stress conditions. These results suggest that the failure of the HK-2 cel ls to increase hsp 27 and hsp 60 levels in response to physical and chemica l stress is because they already possess elevated basal levels of these pro teins. This would indicate that one or more of the genetic events that resu lted in the immortalization of the HK-2 cells also elicited a stress respon se for hsp 27 and hsp 60, but not for hsp 70, stress response family member s. Overall, the results suggest that although there are differences in the regulation of the stress response between the immortal HK-2 and mortal HPT cell lines, as long as these differences are recognized, the HK-2 cell line should be a valuable adjunct to study the stress response of the proximal tubule in general and when exposed to environmental pollutants such as cadm ium.