Abstract
We examined a possible role for heat shock factor-1 (HSF-1) in the negative regulation of HO-1 gene expression in human Hep3B hepatoma cells responding to stimulation with 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) and arsenite. Overexpression of HSF-1 and heat-shock experiments indicated that HSF-1 repressed the 15d-PGJ2-and arsenite-induced HO-1 gene expression through directly binding to the consensus heat shock element (HSE) of the HO-1 gene promoter. In addition, point mutations at specific HSE sequences of the HO-1 promoter-driven luciferase plasmid (pGL2/hHO3.2-Luc) abolished the heat shock- and HSF-1-mediated repression of reporter activity. Overall, it is possible that HSF-1 negatively regulates HO-1 gene expression, and that the HSE present in the -389 to -362 region mediates HSF-1-induced repression of human HO-1 gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Arsenites / pharmacology
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Blotting, Western
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Carcinoma, Hepatocellular / genetics
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Carcinoma, Hepatocellular / metabolism*
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Carcinoma, Hepatocellular / pathology
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Cell Line, Tumor
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DNA-Binding Proteins / physiology*
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Electrophoretic Mobility Shift Assay
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Enzyme Induction / drug effects
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Gene Expression Regulation, Enzymologic / drug effects*
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Genes, Reporter
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Heat Shock Transcription Factors
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Heme Oxygenase (Decyclizing) / biosynthesis*
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Heme Oxygenase (Decyclizing) / genetics
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Heme Oxygenase-1
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Humans
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Luciferases / metabolism
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Membrane Proteins
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Mutagenesis, Site-Directed
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Plasmids
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Point Mutation
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Promoter Regions, Genetic
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Prostaglandin D2 / analogs & derivatives*
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Prostaglandin D2 / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors
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Transcriptional Activation
Substances
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Antineoplastic Agents
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Arsenites
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DNA-Binding Proteins
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Heat Shock Transcription Factors
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Membrane Proteins
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Trans-Activators
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Transcription Factors
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9-deoxy-delta-9-prostaglandin D2
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Luciferases
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HMOX1 protein, human
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Heme Oxygenase (Decyclizing)
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Heme Oxygenase-1
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arsenite
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Prostaglandin D2