Linked Life Data

11675004

Source:http://linkedlifedata.com/resource/pubmed/id/11675004

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2001-10-24
pubmed:abstractText
The major binding site for morphine is the mu opioid receptor (MOR), which mediates morphine's analgesic and euphoric effects. The MOR gene is highly regulated at the level of transcription. The present study examined DNA-protein interactions in the human MOR (hMOR) -500 to -292 promoter region, and tested whether chronic opioid drug treatment could modulate these DNA-protein interactions. 5'-deletion and transient transfection assays in SK-N-SH cells revealed four regions that activated hMOR gene transcription. A 60 bp sequence (-351 to -292) upstream of the proximal transcription initiation site (-252) contained cis-elements required for basal promoter activity. Sp1 and Sp3 bound to this 60 bp region, which was confirmed by electromobility shift assays using a Sp1 consensus oligo as competitor and specific antibodies against Sp1 and Sp3. Methylation interference analysis localized the Sp1 binding site to the sequence CCCTCCTCCC (-310 to -301) and also suggested that additional transcription factors, other than Sp1-related proteins, contacted the -321 to -301 sequence. Moreover, the binding of Sp1/Sp3 to the hMOR promoter was significantly enhanced by chronic exposure to [D-Ala(2), N-Me-Phe(4), Gly(5)-ol] enkephalin (DAMGO), a selective MOR agonist, and this effect was attenuated specifically by pretreatment with a MOR antagonist, naloxone. Taken together, the present studies demonstrated, for the first time, that the binding of Sp1/Sp3 to the hMOR proximal promoter could be modulated by chronic DAMGO treatment. Such enhanced binding of Sp1/Sp3 to the promoter may lead to a functional change in hMOR gene transcription.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0378-1119
pubmed:author
pubmed:issnType
Print
pubmed:day
22
pubmed:volume
274
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
119-28
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11675004-Base Sequence, pubmed-meshheading:11675004-Binding Sites, pubmed-meshheading:11675004-DNA, pubmed-meshheading:11675004-DNA Methylation, pubmed-meshheading:11675004-DNA-Binding Proteins, pubmed-meshheading:11675004-Electrophoretic Mobility Shift Assay, pubmed-meshheading:11675004-Enkephalin, Ala(2)-MePhe(4)-Gly(5)-, pubmed-meshheading:11675004-Humans, pubmed-meshheading:11675004-Luciferases, pubmed-meshheading:11675004-Molecular Sequence Data, pubmed-meshheading:11675004-Nuclear Proteins, pubmed-meshheading:11675004-Plasmids, pubmed-meshheading:11675004-Promoter Regions, Genetic, pubmed-meshheading:11675004-Protein Binding, pubmed-meshheading:11675004-Receptors, Opioid, mu, pubmed-meshheading:11675004-Regulatory Sequences, Nucleic Acid, pubmed-meshheading:11675004-Sp1 Transcription Factor, pubmed-meshheading:11675004-Sp3 Transcription Factor, pubmed-meshheading:11675004-Transcription Factors, pubmed-meshheading:11675004-Tumor Cells, Cultured
pubmed:year
2001
pubmed:articleTitle
Binding of Sp1/Sp3 to the proximal promoter of the hMOR gene is enhanced by DAMGO.
pubmed:affiliation
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 4602-5121, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.