Enhanced protein denaturation in indomethacin-treated cells.
Indomethacin, a potent anti-inflammatory drug, activates the DNA-binding activity of human heat shock transcription factor 1 (HSF1), but this is insufficient to elevate heat shock gene expression. However, indomethacin pretreatment leads to a complete heat shock response at temperatures that are by themselves insufficient. Here, we showed that the heat-induced loss of enzymatic activity of a nuclear or a cytoplasmic luciferase expressed in murine cells was enhanced when cells had been pretreated with indomethacin. Additionally, in these cells the 70-kDa constitutive heat shock protein exhibited an enhanced aggregation in the presence of indomethacin. Similarly an increase in the aggregation of beta-galactosidase was observed. These data suggest that indomethacin at moderate temperatures accelerates the presence of denatured proteins in the cell, thus lowering the temperature threshold for a heat shock response.
Roussou
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Laboratory of General Biology, Medical School, University of Ioannina, Greece. eroussou@cc.uoi.gr
Nguyen
v T
vT
Pagoulatos
G N
GN
Bensaude
O
O
D016475:3T3 Cells / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D002999:Clone Cells / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000502:physiology*; D018840:HSP70 Heat-Shock Proteins / Q000737:chemistry / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006358:Hot Temperature; D007213:Indomethacin / Q000494:pharmacology*; D051379:Mice; D011489:Protein Denaturation / Q000187:drug effects*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013312:Stress, Physiological / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004268:DNA-Binding Proteins; C000619706:HSF1 protein, human; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D007213:Indomethacin