Linked Life Data

19897079

Source:http://linkedlifedata.com/resource/pubmed/id/19897079

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pubmed-article:19897079pubmed:abstractTextThe 32-kDa dopamine- and adenosine 3',5'-monophosphate-regulated phosphoprotein (DARPP-32) is recognized to be critical to the pathogenesis of drug addiction. Opiates via the mu-receptor act on the dopaminergic system in the brain and modulates the expression of DARPP-32 phosphoprotein which is an important mediator of the activity of the extracellular signal-regulated kinase (ERK) signaling cascades, the activation of which represents an exciting nexus for drug-induced changes in neural long-term synaptic plasticity. Silencing of DARPP-32 using an siRNA against DARPP-32 may provide a novel gene therapy strategy to overcome drug addiction. In this study, we investigated the effect of the opiate (heroin) on D1 receptor (D1R) and DARPP-32 expression and additionally, evaluated the effects of DARPP-32-siRNA gene silencing on protein phosphatase-1 (PP-1), ERK, and cAMP response element-binding (CREB) gene expression in primary normal human astrocytes (NHA) cells in vitro. Our results indicate that heroin significantly upregulated both D1R and DARPP-32 gene expression, and that DARPP-32 silencing in the NHA cells resulted in the significant modulation of the activity of downstream effector molecules such as PP-1, ERK, and CREB which are known to play an important role in opiate abuse-induced changes in long-term neural plasticity. These findings have the potential to facilitate the development of DARPP32 siRNA-based therapeutics against drug addiction.lld:pubmed
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pubmed-article:19897079pubmed:authorpubmed-author:PrasadParas...lld:pubmed
pubmed-article:19897079pubmed:authorpubmed-author:DingHongHlld:pubmed
pubmed-article:19897079pubmed:authorpubmed-author:AalinkeelRavi...lld:pubmed
pubmed-article:19897079pubmed:authorpubmed-author:MahajanSupriy...lld:pubmed
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pubmed-article:19897079pubmed:authorpubmed-author:NairBindukuma...lld:pubmed
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