Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.5.1.19 (NOS)
 7,285 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic pathway injury similar to that observed in Parkinson's disease. Many hypotheses have been proposed to explain the mechanisms underlying MPTP neurotoxicity. Previous work showed that the inhibitor of neuronal nitric oxide synthase (nNOS) might produce protection against MPTP-induced dopaminergic toxicity. To exactly test the role of NO in MPTP neurotoxicity, we examined the effect of nNOS inhibitor 7-nitroindazole, in comparison with that of nonselective NOS inhibitor (L-NAME), immunosuppressant (FK-506), monoamine oxidase (MAO) inhibitors (clorgyline and pargyline), N-methyl-D-aspartate receptor antagonist (MK-801) and Ca2+ antagonist (amlodipine). Among seven compounds, 7-nitroindazole produced dose-dependent protection against MPTP-induced depletion of striatal dopamine and its metabolite 3,4-dihydroxyphenyl acetic acid (DOPAC) in mice. Clorgyline and pargyline also showed a significant effect on MPTP-induced dopamine depletion in the mouse striatum. However, both compounds did not protect against MPTP-induced depletion of striatal DOPAC Our immunohistological study with tyrosine hydroxylase (TH) and microtuble-associated protein 2 (MAP 2) showed that 7-nitroindazole or pargyline can protect against MPTP-induced depletion of TH and MAP 2 immunostained neurons in the substantia nigra. Furthermore, these compounds reduced a marked increase in GFAP-positive astrocytes of the mouse striatum after MPTP treatments. The present study demonstrates that nNOS inhibitor 7-nitroindazole as well as MAO inhibitors clorgyline and pargyline can produce dose-dependent neuroprotection against the dopaminergic neurotoxicity of MPTP. However, nonselective NOS inhibitor L-NAME, immunosuppressant FK-506, NMDA receptor antagonist MK-801 and Ca2+ antagonist amlodipine did not show a beneficial effect on MPTP neurotoxicity.
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PMID:Role of nitric oxide synthase against MPTP neurotoxicity in mice. 1239 1

We investigated the immunohistochemical alterations of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), tyrosine hydroxylase (TH), microtubule-associated protein 2a,b (MAP 2), glial fibrillary acidic protein (GFAP), parvalbumin (PV), and dopamine transporter (DAT) in the striatum and substantia nigra following the application of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. TH-, MAP 2- and DAT-immunoreactive cells were decreased gradually in the striatum and substantia nigra from 1 day up to 7 days after MPTP treatment, as well as the reduction of the striatal dopamine, DOPAC and HVA content. The number of GFAP-immunoreactive astrocytes increased gradually in the striatum and substantia nigra from 1 day up to 7 days after MPTP treatment. Striatal nNOS-immunoreactive cells were unchanged in MPTP-treated mice. In the substantia nigra, intense immunoreactivity of nNOS-positive cells increased 5 hr after MPTP treatment. Thereafter, the immunoreactivity of nNOS-positive cells decreased gradually from 1 day up to 7 days after MPTP treatment. eNOS-immunopositive cells were unchanged in the striatum and substantia nigra. These results demonstrate that nNOS may play a key role in the development of MPTP neurotoxicity. Our findings also indicate that MPTP can cause the functional damage of interneurons in the substantia nigra, but not in the striatum.
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PMID:Cerebral alterations in a MPTP-mouse model of Parkinson's disease--an immunocytochemical study. 1452 25