| http://purl.uniprot.org/citations/14565778 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/14565778 | http://www.w3.org/2000/01/rdf-schema#comment | "Reactive oxygen species (ROS) and reactive nitrogen species (RNS), particularly peroxynitrite, have been implicated as key participants in the dopaminergic neurotoxicity of 1-methyl-4-phenylpyridinium (MPP(+)). However, on the basis of available information, it is not clear whether the MPP(+)-induced overproduction of ROS and RNS occurs in the intraneuronal and/or extracellular compartment. Early steps in the neurotoxic mechanism evoked by MPP(+) include a profound dopaminergic energy impairment, which mediates a massive release of dopamine (DA), glutathione (GSH), and cysteine (CySH). In the event that MPP(+) mediates extracellular generation of ROS (such as superoxide and/or hydroxyl radicals) and/or peroxynitrite, released DA, GSH, and CySH should be oxidized forming thioethers of DA and disulfides. Using microdialysis experiments in which MPP(+) was perfused into the striatum of awake rats, the present study was unable to detect the presence of such biomarkers of extracellular ROS and/or RNS generation. However, MPP(+) induced a transient, concentration-dependent rise of extracellular l-3,4-dihydroxyphenylalanine (l-DOPA), identified on the basis of dialysate analysis using several HPLC methods and its conversion to DA by purified l-DOPA decarboxylase (DDC). Methamphetamine (30 mg/kg, i.p.) similarly caused a significant but transient rise of l-DOPA in the rat striatum. Antioxidants such as salicylate and mannitol had no effect on the MPP(+)-mediated elevation of extracellular l-DOPA, suggesting that it is not formed by nonenzymatic hydroxylation of l-tyrosine by ROS or RNS. Rather, in vivo, but not in vitro, MPP(+) caused rapid inhibition of DDC, which appears to result in intraneuronal accumulation and subsequent release of l-DOPA. Because l-DOPA can mediate l-glutamate release, as well as be an excitotoxin, the possibility is raised that l-DOPA may play a role in the dopaminergic neurotoxicity of MPP(+)."xsd:string |
| http://purl.uniprot.org/citations/14565778 | http://purl.org/dc/terms/identifier | "doi:10.1021/tx030015l"xsd:string |
| http://purl.uniprot.org/citations/14565778 | http://purl.uniprot.org/core/author | "Han J."xsd:string |
| http://purl.uniprot.org/citations/14565778 | http://purl.uniprot.org/core/author | "Foster S.B."xsd:string |
| http://purl.uniprot.org/citations/14565778 | http://purl.uniprot.org/core/author | "Dryhurst G."xsd:string |
| http://purl.uniprot.org/citations/14565778 | http://purl.uniprot.org/core/author | "Wrona M.Z."xsd:string |
| http://purl.uniprot.org/citations/14565778 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/14565778 | http://purl.uniprot.org/core/name | "Chem Res Toxicol"xsd:string |
| http://purl.uniprot.org/citations/14565778 | http://purl.uniprot.org/core/pages | "1372-1384"xsd:string |
| http://purl.uniprot.org/citations/14565778 | http://purl.uniprot.org/core/title | "The parkinsonian neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) mediates release of l-3,4-dihydroxyphenylalanine (l-DOPA) and inhibition of l-DOPA decarboxylase in the rat striatum: a microdialysis study."xsd:string |
| http://purl.uniprot.org/citations/14565778 | http://purl.uniprot.org/core/volume | "16"xsd:string |
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