Activation and regulation of Hsp32 and Hsp70.
Endothelial cells (EC) play a key role in the propagation of inflammatory responses. Better understanding of inflammatory processes in EC might provide new ways of controlling inflammation. We report here that the known antioxidant pyrrolidinedithiocarbamate (PDTC) leads to time and dose dependent activation of heat-shock protein 70 (Hsp70) as well as Hsp32 in EC. We further demonstrate that PDTC activates heat-shock factor 1 (HSF1), one of several transcription factor involved in the upregulation of heat-shock proteins. And more importantly, we demonstrate that Hsp32 as well as Hsp70 can be upregulated independently of the transcription factor nuclear factor kappaB (NF-kappaB). The presented data provide further insight into the mechanism of Hsp32 and Hsp70 regulation, as well as further distinguishing these genes from other so called 'protective genes' whose upregulation depends on the activation of NF-kappaB. These findings indicate that Hsp32 and Hsp70 might be ideal candidates among protective genes. Hsp32 and Hsp70 provide many desirable protective effects but, being independent of NF-kappaB, would leave open the option to interfere with the upregulation of proinflammatory genes by modulating the activation of NF-kappaB.
Stuhlmeier
K M
KM
Center for Immunobiology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. karlms@excite.com
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D020672:I-kappa B Proteins; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives / Q000494:pharmacology; D013552:Swine; D013859:Thiocarbamates / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D020672:I-kappa B Proteins; D016328:NF-kappa B; D013859:Thiocarbamates; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C066229:prolinedithiocarbamate; D000072000:NF-KappaB Inhibitor alpha; D011392:Proline; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1