Oxidative injury rapidly activates the heat shock transcription factor but fails to increase levels of heat shock proteins.
When cells are exposed to heat shock, heavy metals, amino acid analogues, and other stresses, the heat shock transcription factor (HSF) is activated. The HSF then binds to the promoter of the heat shock genes, stimulating transcription of the heat shock proteins. Here, we demonstrate that exposure of NIH-3T3 cells to oxidants (H2O2 or menadione) also causes activation of the HSF. This activation is not blocked by inhibitors of protein synthesis (cycloheximide) or by inhibitors of protein kinases (2-aminopurine or genistein). In addition, the oxidant activated HSF is located in the nucleus of the cells. However, oxidant activation of the HSF does not result in the accumulation of hsp70 mRNA or of heat shock proteins. This is in contrast to the accumulation of heat shock proteins seen after heat shock activation of the HSF. This suggests that oxidant induced activation of HSF binding may have a function different from that of heat induced activation of HSF binding.
Bruce
J L
JL
Joint Center for Radiation Therapy, Dana-Farber Cancer Institute, Boston, Massachusetts 02115.
Price
B D
BD
Coleman
C N
CN
Calderwood
S K
SK
D016475:3T3 Cells / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015152:Blotting, Northern; D004268:DNA-Binding Proteins / Q000235:genetics*; D004586:Electrophoresis; D005786:Gene Expression Regulation / Q000187:drug effects; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006361:Heating; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000032:analysis; D017382:Reactive Oxygen Species / Q000633:toxicity*; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology; D014812:Vitamin K / Q000633:toxicity
D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D014812:Vitamin K; D006861:Hydrogen Peroxide