Enhanced protein denaturation in indomethacin-treated cells

Indomethacin, a potent anti-inflammatory drug, activates the DNA-binding ac tivity of human heat shock transcription factor 1 (HSF1), but this is insuf ficient to elevate heat shock gene expression. However, indomethacin pretre atment leads to a complete heat shock response at temperatures that are by themselves insufficient. Here, we showed that the heat-induced loss of enzy matic activity of a nuclear or a cytoplasmic luciferase expressed in murine cells was enhanced when cells had been pretreated with indomethacin. Addit ionally, in these cells the 70-kDa constitutive heat shock protein exhibite d an enhanced aggregation in the presence of indomethacin. Similarly an inc rease in the aggregation of beta-galactosidase was observed. These data sug gest that indomethacin at moderate temperatures accelerates the presence of denatured proteins in the cell, thus lowering the temperature threshold fo r a heat shock response.