Protective effect of thioredoxin upon NO-mediated cell injury in THP1 monocytic human cells

Autor:	O. Negre, E. E. Wollman, D. Fradelizi, P. J. Ferret, E. Soum
Rok vydání:	2000
Předmět:	U937 cell Thioredoxin reductase Cell Cell Biology Transfection Biology Biochemistry Molecular biology Superoxide dismutase medicine.anatomical_structure Cell culture medicine biology.protein Cytotoxic T cell Thioredoxin Molecular Biology
Zdroj:	Biochemical Journal. 346:759-765
ISSN:	1470-8728 0264-6021
DOI:	10.1042/bj3460759
Popis:	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 D3 (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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_________::5ade5161181d51c88d292f9e242d3cd3 https://doi.org/10.1042/bj3460759 Zobrazit plný text záznamu