title: Gold(I) complexes determine apoptosis with limited oxidative stress in Jurkat T cells.
abstract: In Jurkat T cells, S-triethylphosphinegold(I)-2,3,4,6-tetra-O-acetyl-1-thio-beta-d-glucopyranoside (auranofin) and triethylphosphine gold(I) chloride (TepAu) induced apoptosis, as estimated by DNA fragmentation and visualised by fluorescence microscopy. Apoptosis was characterised by mitochondrial cytochrome c release which was not prevented by cyclosporin A. Apoptosis appeared to be triggered by inhibition exerted by gold(I) compounds on the cytosolic and mitochondrial isoforms of thioredoxin reductase, which determined a definite increase in hydrogen peroxide, whereas glutathione and its redox state were not modified. Total thiols showed a slight decrease, particularly in the presence of auranofin. However, no significant lipid peroxidation or nitric oxide formation were observed after incubation with gold(I) complexes, indicating that the cells had not been subjected to extensive oxidative stress. Interestingly, the gold(I) compound aurothiomalate was poorly effective, both in inhibiting thioredoxin reductase and in inducing apoptosis. These results demonstrate that the increased production of hydrogen peroxide determines an oxidative shift responsible for the occurrence of apoptosis and not involving lipid peroxidation.
authors.affiliation: Department of Biological Chemistry, University of Padova, Viale G. Colombo 3, Padova, Italy.
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Rigobello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Folda
authors.forename: Barbara
authors.initials: B
authors.lastname: Dani
authors.forename: Roberta
authors.initials: R
authors.lastname: Menabò
authors.forename: Guido
authors.initials: G
authors.lastname: Scutari
authors.forename: Alberto
authors.initials: A
authors.lastname: Bindoli
mesh_terms: D018501:Antirheumatic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001310:Auranofin / Q000494:pharmacology*; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D019169:Jurkat Cells; D015227:Lipid Peroxidation / Q000187:drug effects; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D050607:Organogold Compounds / Q000494:pharmacology*; D018384:Oxidative Stress; D010720:Phosphines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D050607:Organogold Compounds; D010720:Phosphines; D017382:Reactive Oxygen Species; D001310:Auranofin; C016797:triethyl phosphine gold; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D013880:Thioredoxin-Disulfide Reductase