Linked Life Data

19996297

Source:http://linkedlifedata.com/resource/pubmed/id/19996297

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-2-23
pubmed:abstractText
beta-Arrestins, regulators of G protein-coupled receptor-G protein coupling and receptor desensitization and internalization, function also as scaffolding proteins mediating cellular signaling events. beta-Arrestin1 was previously implicated by us in the pathophysiology of depression and in the mechanism of action of antidepressants (ADs). The ubiquitously expressed beta-arrestins1 and 2 are structurally highly homologous. There has been extensive investigation of these two proteins to determine whether they serve different roles in receptor signaling. In this study, we show that treatment of C(6) rat glioma cells with ADs of various types for 3 days resulted in decreased beta-arrestin2 levels. In contrast, beta-arrestin2 mRNA expression was found to be up-regulated by ADs. To unravel the mechanism for these opposite effects several possible beta-arrestin2 post-transcriptional events and modifications were examined. C(6) rat glioma cells transfected with beta-arrestin1-targeted short hairpin RNA showed similar effects of ADs on beta-arrestin2 levels. AD-induced decreases in beta-arrestin2 protein levels were not due to cytosolic membrane translocation. Immunoprecipitation experiments showed that ADs were able to increase coimmunoprecipitation of ubiquitin with beta-arrestin2. AD-induced increases in beta-arrestin2 ubiquitinylation led to its degradation by the proteasomal pathway, as the proteasome inhibitor N-[(phenylmethoxy)carbonyl]-l-leucyl-N-[(1S)-1-formyl-3-methylbutyl]-l-leucinamide (MG-132) prevented antidepressant-induced decreases in beta-arrestin2 protein levels.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
332
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
970-6
pubmed:dateRevised
2011-5-12
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Antidepressants increase ?-arrestin 2 ubiquitinylation and degradation by the proteasomal pathway in C6 rat glioma cells.
pubmed:affiliation
Department of Pharmacology, Ben Gurion University of the Negev, P.O. Box 653, Beer Sheva, Israel 84105.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't