http://www.cnr.it/ontology/cnr/individuo/prodotto/ID174209
Activation of the heat shock factor 1 by serine protease inhibitors. An effect associated with nuclear factor-kB inhibition. (Articolo in rivista)
- Type
- Label
- Activation of the heat shock factor 1 by serine protease inhibitors. An effect associated with nuclear factor-kB inhibition. (Articolo in rivista) (literal)
- Anno
- 1998-01-01T00:00:00+01:00 (literal)
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- Rossi A.(1); Elia G.(1); Santoro M.G.(1,2) (literal)
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- Rivista
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- 1-Institute of Experimental Medicine, Consiglio Nazionale delle Ricerche, Rome,
2-Department of Biology, University of Rome Tor Vergata, Rome, Italy (literal)
- Titolo
- Activation of the heat shock factor 1 by serine protease inhibitors. An effect associated with nuclear factor-kB inhibition. (literal)
- Abstract
- Heat shock proteins (HSPs) have a cytoprotective role in several human diseases, including ischemia and viral infection. Nuclear factor-?B (NF-?B) is a critical regulator of inflammation and virus replication. Here we report that a class of serine protease inhibitors with NF-?B-inhibitory activity are potent HSP inducers via activation of heat shock transcription factor 1 (HSF1) in human cells. 3,4-Dichloroisocoumarin, the most effective compound, rapidly induces HSF1 DNA binding activity and phosphorylation, leading to transcription and translation of heat shock genes for a period of several hours. HSF1 activation is independent of de novo protein synthesis and is correlated in a concentration- and time-dependent manner with NF-?B inhibition. Cysteine protease inhibitors E64 and calpain inhibitor II, which do not block NF-?B activation, do not induce HSF DNA binding activity. HSP induction by 3,4-dichloroisocoumarin is associated with antiviral activity during rhabdovirus infection. These results identify a new class of HSP inducers and indicate a link between the regulatory pathways of HSF and NF-?B, suggesting novel strategies to simultaneously switch on cytoprotective genes and down-regulate inflammatory and viral genes. (literal)
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