Summary.
We investigated the effect of nitric oxide (NO) on iron-induced neuronal damage. Incubation of PC12 cells after the addition of FeCl2 in-duced rapid increases (within 1 hr) in lipid peroxidation and a concentration (0.1–2 mM)-dependent decrease in cell viability at 48 hr, both of which were blocked by deferoxamine and 2-methyl-6-(p-methoxyphenyl)-3,7-dihydroimidazo[1,2-a]pyrazine-3-one hydrochloride (MCLA) (a superoxide scavenger) but not by mannitol (a hydroxyl radical scavenger). Iron-induced cytotoxicity was also antagonized by superoxide dismutase with catalase. On the other hand, the NO donors S-nitroso-N-acetylpenicillamine (SNAP), 3-{(±)-(E)-ethyl-2′-[(E)-hydroxylamino]-5-nitro-3-hexenecarbomoyl}-pyridine (NOR-4), and 2,2′-(hydroxynitrosohydrazono)bis-ethanamine (NOC-18) decreased cell viability 48 hr after addition without increasing lipid peroxidation. However, when added with 1 mM FeCl2, NO donors including NOC-18, SNAP and NOR-4 (0.1–1 mM) inhibited lipid peroxidation in a concentration-dependent manner and suppressed cell death at lower concentrations. Addition of MCLA and NOC-18 also suppressed decreases in iron-induced [3H]thymidine incorporation. In rat brain homogenate, NOC-18 and SNAP both suppressed iron-induced lipid peroxidation. These findings suggest that NO has a dual effect on neuronal viability and can act as an antioxidant which protects neurons from iron-induced damage.
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Received February 17, 1998; accepted March 23, 1999
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Nara, K., Konno, D., Uchida, J. et al. Protective effect of nitric oxide against iron-induced neuronal damage. J Neural Transm 106, 835–848 (1999). https://doi.org/10.1007/s007020050204
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DOI: https://doi.org/10.1007/s007020050204