Two Naturally Occurring Terpenes, Dehydrocostuslactone and Costunolide, Decrease Intracellular GSH Content and Inhibit STAT3 ActivationReport as inadecuate




Two Naturally Occurring Terpenes, Dehydrocostuslactone and Costunolide, Decrease Intracellular GSH Content and Inhibit STAT3 Activation - Download this document for free, or read online. Document in PDF available to download.

The main purpose of the present study is to envisage the molecular mechanism of inhibitory action ofdehydrocostuslactone DCE andcostunolide CS, two naturally occurring sesquiterpene lactones, towards the activation of signal transducer and activator of transcription 3 STAT3. We report that, in human THP-1 cell line, they inhibit IL-6-elicited tyrosine phosphorylation of STAT3 and its DNA binding activity with EC50 of 10 µM with concomitantdown-regulation ofthe phosphorylation of the tyrosine Janus kinases JAK1, JAK2 and Tyk2. Furthermore, these compounds that contain an α-β-unsatured carbonyl moiety and function as potent Michael reaction acceptor, induce a rapid drop in intracellular glutathione GSH concentration by direct interaction with it, thereby triggering S-glutathionylation of STAT3. Dehydrocostunolide HCS, the reduced form of CS lacking only the α-β-unsaturated carbonyl group, fails to exert any inhibitory action. Finally, the glutathione ethylene ester GEE, the cell permeable GSH form, reverts the inhibitory action of DCE and CS on STAT3 tyrosine phosphorylation. We conclude that these two sesquiterpene lactones are able to induce redox-dependent post-translational modification of cysteine residues of STAT3 protein in order to regulate its function.



Author: Elena Butturini, Elisabetta Cavalieri, Alessandra Carcereri de Prati, Elena Darra, Antonella Rigo, Kazuo Shoji, Norie Murayama, H

Source: http://plos.srce.hr/



DOWNLOAD PDF




Related documents