Linked Life Data

12112414

Source:http://linkedlifedata.com/resource/pubmed/id/12112414

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2002-7-11
pubmed:abstractText
The psychostimulants cocaine and amphetamine increase expression of the immediate early gene (IEG) c-fos indirectly, via D1 dopamine receptor activation. To determine whether dopamine transporter substrates and inhibitors can affect c-Fos expression directly, we investigated their effects on c-Fos protein and c-fos mRNA in HEK-293 (HEK) cells transfected with the human dopamine transporter (hDAT). In untransfected HEK cells, methylphenidate and cocaine produced a small but statistically significant increase in c-Fos, whereas dopamine and amphetamine did not. In hDAT cells, DAT substrates (dopamine, amphetamine) increased c-Fos immunoreactivity 6- and 3-fold (respectively). The DAT inhibitors cocaine, methylphenidate, and bupropion also increased c-Fos approximately 3-fold in hDAT cells. If coincubated with dopamine, the inhibitors attenuated dopamine-induced c-Fos in hDAT cells. The magnitude of c-fos mRNA induction by substrates and inhibitors paralleled induction of c-Fos protein immunoreactivity. The results indicate that substrates or inhibitors of the DAT can trigger induction of IEG expression in the absence of D1 dopamine receptor. For substrates, IEG induction is DAT-dependent, but for certain DAT inhibitors the cellular response can be elicited in the absence of the DAT in HEK cells. Oxidative stress may partly, but not fully, account for the DA-induced c-Fos induction as an inhibitor of oxidative stress Trolox C, attenuated DA-induced c-Fos induction. Protein kinase C (PKC) may also partially account for c-Fos induction as a specific inhibitor of PKC Bisindolylmaleimide I (BIS) attenuated DA-induced c-Fos by 50%. DAT substrate and inhibitor effects on IEGs, other fos-related antigens, and possible mechanisms that contribute to c-Fos induction warrant investigation in presynaptic neurons as a potential contribution to the long-term effects of psychostimulants.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Amphetamine, http://linkedlifedata.com/resource/pubmed/chemical/Cocaine, http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Plasma Membrane Transport..., http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Uptake Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Modulators, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Transport Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Methylphenidate, http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos, http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger, http://linkedlifedata.com/resource/pubmed/chemical/SLC6A3 protein, human
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0887-4476
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
52-65
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Dopamine transporter-dependent induction of C-Fos in HEK cells.
pubmed:affiliation
Harvard Medical School, New England Regional Primate Research Center, Southborough, Massachusetts 01772-9102, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.