Gold(I) complexes determine apoptosis with limited oxidative stress in Jurkat T cells.
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.
Rigobello
Maria Pia
MP
Department of Biological Chemistry, University of Padova, Viale G. Colombo 3, Padova, Italy.
Folda
Alessandra
A
Dani
Barbara
B
Menabò
Roberta
R
Scutari
Guido
G
Bindoli
Alberto
A
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
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