Biological effects of pramipexole on dopaminergic neuron-associated genes: relevance to neuroprotection.
Identifieur interne : 000202 ( PubMed/Corpus ); précédent : 000201; suivant : 000203Biological effects of pramipexole on dopaminergic neuron-associated genes: relevance to neuroprotection.
Auteurs : Tianhong Pan ; Wenjie Xie ; Joseph Jankovic ; Weidong LeSource :
- Neuroscience letters [ 0304-3940 ] ; 2005.
English descriptors
- KwdEn :
- Benzothiazoles, Cell Line, Tumor, Dopamine (biosynthesis), Dopamine (genetics), Dopamine Plasma Membrane Transport Proteins, Dose-Response Relationship, Drug, Humans, Membrane Glycoproteins (biosynthesis), Membrane Glycoproteins (genetics), Membrane Transport Proteins (biosynthesis), Membrane Transport Proteins (genetics), Nerve Tissue Proteins (biosynthesis), Nerve Tissue Proteins (genetics), Neurons (drug effects), Neurons (metabolism), Neuroprotective Agents (pharmacology), Thiazoles (pharmacology).
- MESH :
- chemical , biosynthesis : Dopamine, Membrane Glycoproteins, Membrane Transport Proteins, Nerve Tissue Proteins.
- chemical , genetics : Dopamine, Membrane Glycoproteins, Membrane Transport Proteins, Nerve Tissue Proteins.
- chemical , pharmacology : Neuroprotective Agents, Thiazoles.
- chemical : Benzothiazoles, Dopamine Plasma Membrane Transport Proteins.
- drug effects : Neurons.
- metabolism : Neurons.
- Cell Line, Tumor, Dose-Response Relationship, Drug, Humans.
Abstract
Pramipexole (PRX) is a non-ergot dopamine (DA) D2/D3 receptor agonist. Experimental studies have provided evidence that PRX may exert neuroprotective effects on the nigro-striatal system. Recent studies have demonstrated a slower decline of DAT density in Parkinson's disease patients treated with PRX as measured by SPECT. The aim of this study is to determine whether PRX has direct biological effects on DAergic neuron-associated genes expression, including DAT, VMAT2, and Nurr1. The human neuroblastoma SH-SY5Y cells were treated with PRX for various time periods and harvested to measure the mRNA and protein products of these genes. Treatment with PRX at 10 microM significantly increased DAT mRNA levels by 54-130% in 4-8 h, VMAT2 mRNA levels by 34% in 4 h, and Nurr1 mRNA levels by 31-39% in 2-4 h, which was the earliest induction among these three genes. The protein levels of DAT, VMAT2, and Nurr1 were markedly increased after PRX treatment, among which the increase of Nurr1 protein level was the highest at first 2 h treatment of PRX. Nafadotride, a D3 DA receptor antagonist, blocked the increase of Nurr1 gene expression induced by PRX, while eticlopride, a D2 DA receptor antagonist, didn't show this effect. Our findings that PRX has biological regulatory effects on DAergic neuron-associated genes may explain both the slower decline of imaged DAT and the neuroprotective effect of PRX. Furthermore, our results suggest that the induction of Nurr1 gene expression by PRX may be mediated by D3 DA receptor.
DOI: 10.1016/j.neulet.2004.11.080
PubMed: 15740846
Links to Exploration step
pubmed:15740846Le document en format XML
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<author><name sortKey="Pan, Tianhong" sort="Pan, Tianhong" uniqKey="Pan T" first="Tianhong" last="Pan">Tianhong Pan</name>
<affiliation><nlm:affiliation>Department of Neurology, Parkinson Disease Research Laboratory, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.</nlm:affiliation>
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<author><name sortKey="Xie, Wenjie" sort="Xie, Wenjie" uniqKey="Xie W" first="Wenjie" last="Xie">Wenjie Xie</name>
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<author><name sortKey="Jankovic, Joseph" sort="Jankovic, Joseph" uniqKey="Jankovic J" first="Joseph" last="Jankovic">Joseph Jankovic</name>
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<author><name sortKey="Le, Weidong" sort="Le, Weidong" uniqKey="Le W" first="Weidong" last="Le">Weidong Le</name>
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<front><div type="abstract" xml:lang="en">Pramipexole (PRX) is a non-ergot dopamine (DA) D2/D3 receptor agonist. Experimental studies have provided evidence that PRX may exert neuroprotective effects on the nigro-striatal system. Recent studies have demonstrated a slower decline of DAT density in Parkinson's disease patients treated with PRX as measured by SPECT. The aim of this study is to determine whether PRX has direct biological effects on DAergic neuron-associated genes expression, including DAT, VMAT2, and Nurr1. The human neuroblastoma SH-SY5Y cells were treated with PRX for various time periods and harvested to measure the mRNA and protein products of these genes. Treatment with PRX at 10 microM significantly increased DAT mRNA levels by 54-130% in 4-8 h, VMAT2 mRNA levels by 34% in 4 h, and Nurr1 mRNA levels by 31-39% in 2-4 h, which was the earliest induction among these three genes. The protein levels of DAT, VMAT2, and Nurr1 were markedly increased after PRX treatment, among which the increase of Nurr1 protein level was the highest at first 2 h treatment of PRX. Nafadotride, a D3 DA receptor antagonist, blocked the increase of Nurr1 gene expression induced by PRX, while eticlopride, a D2 DA receptor antagonist, didn't show this effect. Our findings that PRX has biological regulatory effects on DAergic neuron-associated genes may explain both the slower decline of imaged DAT and the neuroprotective effect of PRX. Furthermore, our results suggest that the induction of Nurr1 gene expression by PRX may be mediated by D3 DA receptor.</div>
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<Abstract><AbstractText>Pramipexole (PRX) is a non-ergot dopamine (DA) D2/D3 receptor agonist. Experimental studies have provided evidence that PRX may exert neuroprotective effects on the nigro-striatal system. Recent studies have demonstrated a slower decline of DAT density in Parkinson's disease patients treated with PRX as measured by SPECT. The aim of this study is to determine whether PRX has direct biological effects on DAergic neuron-associated genes expression, including DAT, VMAT2, and Nurr1. The human neuroblastoma SH-SY5Y cells were treated with PRX for various time periods and harvested to measure the mRNA and protein products of these genes. Treatment with PRX at 10 microM significantly increased DAT mRNA levels by 54-130% in 4-8 h, VMAT2 mRNA levels by 34% in 4 h, and Nurr1 mRNA levels by 31-39% in 2-4 h, which was the earliest induction among these three genes. The protein levels of DAT, VMAT2, and Nurr1 were markedly increased after PRX treatment, among which the increase of Nurr1 protein level was the highest at first 2 h treatment of PRX. Nafadotride, a D3 DA receptor antagonist, blocked the increase of Nurr1 gene expression induced by PRX, while eticlopride, a D2 DA receptor antagonist, didn't show this effect. Our findings that PRX has biological regulatory effects on DAergic neuron-associated genes may explain both the slower decline of imaged DAT and the neuroprotective effect of PRX. Furthermore, our results suggest that the induction of Nurr1 gene expression by PRX may be mediated by D3 DA receptor.</AbstractText>
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