Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The neuropathological hallmark of Parkinson's disease (PD) is the selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). In this study, using a microdialysis technique, we investigated whether an inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitrindazole (7-NI), could protect against DAergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP(+)) in freely moving rats. Experiments were performed over 2 days in three groups of rats: (a) nonlesioned, (b) MPP(+)-lesioned, and (c) 7-NI pretreated MPP(+)-lesioned rats. On day 1, control rats were perfused with an artificial CSF, while 1 mM MPP(+) was infused into the striatum for 10 min in the other two groups. The infusion of the MPP(+) produced a neurotoxic damage of the SNc DA neurons and increased striatal DA levels. On day 2, 1 mM MPP(+) was reperfused for 10 min into the striata of each rat group and DA levels were measured as an index of neuronal cell integrity. The limited rise of DA following MPP(+) reperfusion in the MPP(+)-lesioned rats was due to toxin-induced neuronal loss and was reversed by pretreatment with 7-NI (50 mg/kg, intraperitoneally) on day 1, indicating a neuroprotective effect by inhibiting NO formation. These results indicate that neuronally derived NO partially mediates MPP(+)-induced neurotoxicity. The similarity between the MPP(+) model and PD suggests that NO may play a significant role in its etiology.
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PMID:7-nitroindazole protects striatal dopaminergic neurons against MPP+-induced degeneration: an in vivo microdialysis study. 1726 89

This study investigated the expression and functional roles of rat plasma membrane monoamine transporter (rPMAT) in the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier by using in vitro brain barrier model cells (TR-BBB13 and TR-CSFB3 cells) and multiple in vivo experimental techniques. Quantitative reverse transcription-polymerase chain reaction analysis showed relatively high expression of rPMAT mRNA in TR-BBB13 and TR-CSFB3 cells. 1-Methyl-4-phenylpyridinium (MPP(+) ) was transported into rPMAT-expressing cells in a sodium-independent manner. [(3) H]MPP(+) was taken up concentration dependently by TR-BBB13 and TR-CSFB3 cells with K(m) values similar to that of rPMAT-expressing cells. [(3) H]MPP(+) transports into these cells were markedly inhibited by serotonin, dopamine, and cationic drugs. rPMAT small interfering RNA (siRNA) significantly suppressed the [(3) H]MPP(+) uptake by TR-BBB13 cells. Intracerebrally injected [(3) H]MPP(+) was eliminated from the brain parenchymal region, whereas brain [(3) H]MPP(+) uptake did not increase with time during in situ brain perfusion, suggesting that the brain-to-blood transport across the BBB predominates over the blood-to-brain transport. Brain microdialysis studies revealed that the elimination across the BBB was significantly decreased by coperfusion of unlabelled MPP(+) , serotonin, or dopamine. [(3) H]MPP(+) was also eliminated from the CSF. These findings suggest that PMAT in brain barriers functions as the brain-to-blood transporter to regulate brain concentrations of organic cations including monoamines and cationic neurotoxins.
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PMID:Functional characterization of rat plasma membrane monoamine transporter in the blood-brain and blood-cerebrospinal fluid barriers. 2153 54

The hematopoietic cytokines erythropoietin (Epo) and granulocyte-colony stimulating factor (G-CSF) provide neuroprotection in several in vitro and in vivo models of Parkinson's disease (PD). The molecular mechanism by which Epo and G-CSF signals reduce the neuronal death in PD is not clear. Here, we show that in rat pheochromocytoma PC12 cells, Epo and G-CSF efficiently repressed the 1-methyl-4-phenylpyridinium (MPP(+))-induced expression of the proapoptotic protein PUMA (p53 up-regulated modulator of apoptosis). Accordingly, Epo and G-CSF treatment reduced the PC12 cell fraction that underwent apoptosis by MPP(+) treatment and thus improved cell viability. Downregulation of PUMA expression by Epo and G-CSF in MPP(+)-treated PC12 cells seems to be mediated by repression of p53, as the expression of p53 was increased by MPP(+)-treatment and reduced by Epo and G-CSF. Together, these results suggest that the neuroprotective activities of Epo and G-CSF in an experimental model of PD involve the repression of the apoptosis-inducing action of PUMA.
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PMID:Neuroprotective cytokines repress PUMA induction in the 1-methyl-4-phenylpyridinium (MPP(+)) model of Parkinson's disease. 2174 64