title: Protective effect of thioredoxin upon NO-mediated cell injury in THP1 monocytic human cells.
abstract: Although NO has been postulated to play important roles in host defences, it is potentially damaging for exposed cells, including for the macrophages producing the NO. Thus a network of radical acceptors and enzymes is thought to play an important redox-buffering role to protect cells against NO-mediated injury. We examined the properties of the redox systems superoxide dismutase (SOD)/catalase, glutathione (GSH) and thioredoxin (Trx), in regulating the viability of two human monocytic cell lines (THP1 and U937) exposed to the NO-generating compound diethylene triamine-nitric oxide (DETA-NO). We observed that NO-induced cytotoxic effects were time- and dose-dependent towards the two cell lines. After vitamin-induced differentiation in vitro with retinoic acid (RA) and 1,25-dihydroxy vitamin D(3) (VD), termed RA/VD, we observed that THP1 RA/VD cells became more resistant to NO-mediated cytotoxicity whereas the susceptibility of U937 cells was not modified. Using Western blotting and reverse-transcriptase PCR methods, we observed that gene transcription and protein expression of Trx and thioredoxin reductase were significantly increased upon RA/VD treatment and differentiation in THP1 cells. By contrast, SOD/catalase and GSH redox state remained unmodified. Finally, a stable transfectant THP1 line overexpressing Trx was found to be more resistant than THP1 control cells that were untransfected or transfected with an empty plasmid, when exposed to DETA-NO in vitro. In conclusion, we observed an inverse correlation between cell susceptibility to NO damaging effects and Trx expression, suggesting that the Trx system may have important preventative capacities towards NO-mediated cellular injury in monocytic macrophage cells.
authors.affiliation: Laboratoire INSERM Unité 477, Pavillon Hardy, Hôpital Cochin, 27 rue du Fbg St Jacques, 75674 Paris cedex 14, France.
authors.forename: P J
authors.initials: PJ
authors.lastname: Ferret
authors.forename: E
authors.initials: E
authors.lastname: Soum
authors.forename: O
authors.initials: O
authors.lastname: Negre
authors.forename: E E
authors.initials: EE
authors.lastname: Wollman
authors.forename: D
authors.initials: D
authors.lastname: Fradelizi
mesh_terms: D017209:Apoptosis / Q000502:physiology; D001483:Base Sequence; D002374:Catalase / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics; D013879:Thioredoxins / Q000494:pharmacology*; D014212:Tretinoin / Q000494:pharmacology; D015854:Up-Regulation; D014807:Vitamin D / Q000494:pharmacology
chemical_list: D017931:DNA Primers; D012333:RNA, Messenger; D014807:Vitamin D; D009569:Nitric Oxide; D013879:Thioredoxins; D014212:Tretinoin; D002374:Catalase; D013482:Superoxide Dismutase