Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It has been suggested that oxidative stress plays an important role in mediating excitotoxic neuronal death. We have therefore investigated the protective effects of antioxidants against excitotoxic injury in the rat on striatal neurons both in vitro and in vivo. In the first part of the study, we determined whether two different types of antioxidants, the spin trapping agent, alpha-phenyl-tert-butyl nitrone and an inhibitor of lipid peroxidation, U-83836E, could protect cultured striatal neurons against either hypoglycemic injury or N-methyl-D-aspartate-induced excitotoxicity. Dopamine- and cyclic AMP-regulated phosphoprotein, which is enriched in medium-sized spiny neurons, was chosen as a marker for striatal neurons. alpha-Phenyl-t-butyl nitrone and U-83836E both significantly reduced cell death induced by these insults as indicated by an increased number of surviving dopamine- and cyclic AMP-regulated phospho-protein-positive neurons. The two antioxidants also promoted the survival of cultured striatal neurons grown at low cell density under serum-free culture conditions. In an in vivo experiment systemically administered alpha-phenyl-t-butyl nitrone exerted neuroprotective effects in the rat striatum following injection of the excitotoxin quinolinic acid. Apomorphine-induced rotation tests revealed that alpha-phenyl-t-butyl nitrone-treated animals were significantly less asymmetric in their motor behavior than control rats. Treatment with alpha-phenyl-t-butyl nitrone significantly reduced the size of the quinolinic acid-induced striatal lesions, as assessed by the degree of sparing of dopamine- and cyclic AMP-regulated phospho-protein-positive and nicotinamide adenine dinucleotide phosphate-diaphorase-positive neurons, and of microtubule-associated protein-2-immunorective areas. Furthermore, lesion-induced morphological changes in the substantia nigra pars reticulate, i.e. loss of dopamine- and cyclic AMP-regulated phosphoprotein-positive afferent fibers and atrophic changes due to transsynaptic degeneration, were also less extensive in the alpha-phenyl-t-butyl nitrone-treated animals. The results support the hypothesis that oxygen-free radicals contribute to excitotoxic neuronal injury. The in vivo cytoprotective effects of alpha-phenyl-t-butyl nitrone against striatal excitotoxic lesions suggest that antioxidants could be used as potential neuroprotective agents in Huntington's disease, which has been suggested to involve excitotoxicity.
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PMID:Antioxidant treatment protects striatal neurons against excitotoxic insults. 878 41

The aim of the present study was to assess degenerative changes in the nitric oxide (NO) system of basal ganglia in animals with experimentally induced Parkinson's disease. In one procedure, rats were stereotaxically injected with 6-hydroxydopamine (6-OHDA) in the right medial forebrain bundle; in a second procedure, electrodes were implanted in the right substantia nigra pars compacta (SNc). After 15 and 30 days animals were tested for rotational asymmetry induced by apomorphine. Apomorphine induced rotation in lesioned animals, towards the ipsilateral side after electrolytic lesion and towards contralateral side in 6-OHDA animals. Structural deficits in basal ganglia were quantified by nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) histochemistry and by nitric oxide synthase (NOS) immunoreactivity. 6-OHDA and electrolytic lesions induced a significant decrease in the number of NADPH-d/NOS positive cells in the lesion ipsilateral to SNc, in contrast with cell number increase in the ipsilateral dorsal striatum. By contrast, 6-OHDA-treated animals showed a decrease in the number of NOS immunoreactive cells in the contralateral nucleus accumbens. We conclude that populations of NO-synthesizing neurons are differentially regulated in Parkinson's disease induced by different experimental procedures.
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PMID:Effects of electrolytic and 6-hydroxydopamine lesions of rat nigrostriatal pathway on nitric oxide synthase and nicotinamide adenine dinucleotide phosphate diaphorase. 1463 84