Prevention of Dopamine-Induced Cell Death by Thiol Antioxidants: Possible Implications for Treatment of Parkinson's Disease

摘要: Abstract We have recently shown that dopamine (DA) can trigger apoptosis, an active program of cellular self-destruction, in various neuronal cultures and proposed inappropriate activation apoptosis by DA or its oxidation products may initiate nigral cell loss Parkinson's disease (PD). Since toxicity be mediated via generation oxygen-free radical species, we examined whether DA-induced death PC12 cells inhibited antioxidants. found the thiol containing compounds, reduced glutathione (GSH),N-acetyl-cysteine (NAC), dithiothreitol (DTT) were markedly protective, while vitamins C E had lesser no effect. The antioxidants vitamin but not E, prevented autooxidation production dopamine-melanin. Their protective effect has also manifested inhibiting apoptosis; DNA fragmentation was as histochemically thein situend-labeled technique (TUNEL). Intracellular GSH other thiols constitute important natural defense against oxidative stress. depletion addition phoron, a substrate transferase, buthionine sulfoximine (BSO), inhibitor γ-glutamyl transpeptidase, significantly enhanced toxicity. Cotreatment with NAC rescued from toxic BSO + DA, phoron provided only partial protection Our data indicate family antioxidants, are highly effective rescuing apoptosis. Further study mechanisms underlying unique capacity lead to development new neuroprotective therapeutic strategies for PD.