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 vari ety 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 prosta glandins, which contain an alpha,beta-unsaturated carbonyl group in th e cyclopentane ring and possess antiviral activity against several RNA and DNA viruses, were shown to function as signal for HSP synthesis i n a nonstressful situation in a variety of mammalian cells. me now rep ort that 2-cyclopenten-1-one selectively induces the expression of the 70-kDa HSP (HSP70) in human cells, through cycloheximide-sensitive ac tivation of heat shock transcription factor 1 (HSF1). The alpha,beta-u nsaturated carbonyl group is the key structure triggering HSF1 activat ion, 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 an d open new perspectives in the search for novel antiviral and cytoprot ective drugs.