| 18242600 |
Rigobello MP, Folda A, Dani B, Menabo R, Scutari G, Bindoli A: Gold (I) complexes determine apoptosis with limited oxidative stress in Jurkat T cells. Eur J Pharmacol. 2008 Mar 17;582(1-3):26-34. Epub 2008 Jan 4.
In Jurkat T cells, S-triethylphosphinegold (I)-2,3,4,6-tetra-O-acetyl-1-thio-beta-d-glucopyran oside (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. |
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