A role for metals and free radicals in the induction of apoptosis in thymocytes.
Recent reports have implicated a possible but undefined role for reactive oxygen species in the induction and mediation of apoptosis. In the present study, the role of free radicals and metal ions in apoptosis induced in rat thymocytes by dexamethasone and etoposide was examined. Copper chelators, but not iron specific chelators, inhibited apoptosis induced by both these stimuli. Several antioxidants also possessed potent inhibitory effects. We therefore propose that diverse agents may induce apoptosis in thymocytes by a common mechanism involving a copper mediated Fenton reaction, generating site specific hydroxyl radicals, possibly as a result of activation of the redox sensitive transcription factor NF-kappa B.
Wolfe
J T
JT
MRC Toxicology Unit, University of Leicester, UK.
Ross
D
D
Cohen
G M
GM
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000037:antagonists & inhibitors / Q000502:physiology*; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005609:Free Radicals / Q000037:antagonists & inhibitors; D007501:Iron / Q000037:antagonists & inhibitors / Q000502:physiology*; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects; D008297:Male; D009707:Nucleosomes / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D013950:Thymus Gland / Q000166:cytology* / Q000187:drug effects
D000975:Antioxidants; D002614:Chelating Agents; D005609:Free Radicals; D009707:Nucleosomes; D005047:Etoposide; D003300:Copper; D003907:Dexamethasone; D004247:DNA; D007501:Iron