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• W2023648096 endingPage "272" @default.
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• W2023648096 abstract "Nitric oxide (NO) induces cell proliferation or cell death, depending on the cell type involved, the isoform of nitric oxide synthase activated, and its cellular localisation. In neurons, the damaging effect of NO is usually attributed to the highly toxic peroxynitrite, formed by its reaction with superoxide. Peroxynitrite induces DNA damage and consequently the activation of poly (ADP-ribose) polymerase (PARP). This study set out to examine the contribution of peroxynitrite to the damage induced in cerebellar granule neurons (CGNs) by treatment with the NO donor S-nitroso-N-acetylpenicillamine (SNAP), for short (6 h) or prolonged (24 h) exposures. The Alamar blue assay was used to quantify CGN viability, which was also assessed by morphological examination. SNAP (10 µM–1 mM) induced a concentration- and time-dependent reduction of CGN viability, with associated damage to cell bodies and neurite processes evident following 100 µM SNAP treatments. Damage from 6 h exposures was prevented by the presence of haemoglobin (a NO scavenger), uric acid (a peroxynitrite scavenger), melatonin (a non-specific antioxidant), and by cyclosporin A (a permeability transition pore blocker). It was reduced by the PARP-1 inhibitor 3,4-dihydro-5-[4-(1-piperidinyl)butoxyl]-1(2H)-isoquinolinone (DPQ), whilst superoxide dismutase (SOD) potentiated the effects. Following 24 h exposure to SNAP, damage was only partially blocked by haemoglobin, melatonin, cyclosporin A and DPQ, but was not affected by uric acid or SOD. The data suggest that short exposure to NO induces neuronal damage through peroxynitrite produced by its interaction with superoxide, whereas a longer exposure to NO can induce damage partly by a mechanism which is independent of peroxynitrite formation." @default.
• W2023648096 created "2016-06-24" @default.
• W2023648096 creator A5042492055 @default.
• W2023648096 creator A5054574458 @default.
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• W2023648096 date "2008-09-01" @default.
• W2023648096 modified "2023-09-25" @default.
• W2023648096 title "Prolonged exposures of cerebellar granule neurons to S-nitroso-N-acetylpenicillamine (SNAP) induce neuronal damage independently of peroxynitrite" @default.
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• W2023648096 doi "https://doi.org/10.1016/j.brainres.2008.06.109" @default.
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