2-Cyclopenten-1-one, a new inducer of heat shock protein 70 with antiviral activity.
The cytoprotective role of heat shock proteins (HSP) described in variety of human diseases, including ischemia, inflammation, and infection, suggests new therapeutic strategies relying upon the development of drugs that selectively turn on heat shock genes. Cyclopentenone prostaglandins, which contain an alpha, beta-unsaturated carbonyl group in the cyclopentane ring and possess antiviral activity against several RNA and DNA viruses, were shown to function as signal for HSP synthesis in a nonstressful situation in a variety of mammalian cells. We now report that 2-cyclopenten-1-one selectively induces the expression of the 70-kDa HSP (HSP70) in human cells, through cycloheximide-sensitive activation of heat shock transcription factor 1 (HSF1). The alpha, beta-unsaturated carbonyl group is the key structure triggering HSF1 activation. Induction is associated with antiviral activity during infection with vesicular stomatitis virus. These results identify the molecular structure of natural prostaglandins responsible for HSF1 activation and open new perspectives in the search for novel antiviral and cytoprotective drugs.
Rossi
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Institute of Experimental Medicine CNR, Viale K. Marx, 43, 00137 Rome, Italy. santoro@biocell.irmkant.rm.cnr.it
Elia
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Santoro
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D015153:Blotting, Western; D003513:Cycloheximide / Q000494:pharmacology; D003517:Cyclopentanes / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005765:Gastrointestinal Agents / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism; D008970:Molecular Weight; D014407:Tumor Cells, Cultured; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D014779:Virus Replication
D003517:Cyclopentanes; D005765:Gastrointestinal Agents; D018840:HSP70 Heat-Shock Proteins; D004247:DNA; D003513:Cycloheximide; C013905:cyclopentenone