Antioxidant-mediated inhibition of the heat shock response leads to apoptosis

We examined the hypothesis that reactive oxygen species (ROS) contribute to the induction of heat shock proteins (hsps) during stress response, Exposu re of HL-60 human myelocytic cells to 42 degrees C induced both hsp72 and h sp27. In the presence of the antioxidant molecules pyrrolidine dithiocarbam ate or I,10-phenanthroline induction of hsp72 and 27 was significantly decr eased, while N-acetyl-L-cysteine caused a slight reduction, Prevention of h sp induction was associated with heat sensitization and increased caspase a ctivity indicating that the cells were undergoing apoptosis. These data sug gest that BOS contribute to the induction of hsps and furthermore, that hsp induction and apoptosis are mutually exclusive events within the same cell . (C) 1999 Federation of European Biochemical Societies.