Linked Life Data

20843793

Source:http://linkedlifedata.com/resource/pubmed/id/20843793

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
47
pubmed:dateCreated
2010-11-15
pubmed:abstractText
There is increasing evidence that thiazolidinediones (TZDs), antidiabetic compounds that are synthetic ligands for the peroxisome proliferator-activated receptor ? (PPAR?), have cardiovascular effects through as yet poorly defined mechanisms. We tested the effect of two TZD class drugs, rosiglitazone and pioglitazone, on human aortic smooth muscle cell (SMC) expression of insulin-like growth factor-1 receptor (IGF-1R). Both TZDs dose dependently up-regulated IGF-1R protein levels (rosiglitazone, 10 ?mol/liter, 67% increase, n = 4, p < 0.01; pioglitazone, 10 ?mol/liter, 41% increase, n = 4, p < 0.01) and increased IGF-1R signaling activity (36% increase in Akt phosphorylation). However, the endogenous PPAR? ligand, 15-deoxy-?(12,14)-prostaglandin J(2), dose dependently reduced IGF-1R (10 ?mol/liter, 80% decrease, n = 4, p < 0.01), and overexpression of PPAR? using an adenovirus likewise reduced IGF-1R (50% decrease versus SMC infected with control adenovirus), suggesting a PPAR?-independent action of TZDs. All three PPAR? ligands (rosiglitazone, pioglitazone, and 15-deoxy-?(12,14)-prostaglandin J(2)), however, did not change IGF-1R mRNA levels, indicating that their effects were posttranscriptional. Use of bicistronic constructs revealed that TZD induction of IGF-1R translation occurred via internal ribosomal entry. To examine the potential physiological relevance of TZD up-regulation of IGF-1R, we determined the effect of rosiglitazone on oxidized LDL (oxLDL)-induced apoptosis. 20 ?mol/liter of rosiglitazone reduced oxidized LDL-induced apoptosis by 40% and neutralizing antibody to IGF-1R (?IR3) counteracted this rescue, suggesting the rosiglitazone survival effect was, at least in part, mediated by IGF-1R. In conclusion, TZDs markedly up-regulate SMC IGF-1R expression and signaling, likely via a PPAR?-independent mechanism. This novel action of TZDs may play an important role in their cardiovascular effects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
19
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36361-8
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Thiazolidinediones up-regulate insulin-like growth factor-1 receptor via a peroxisome proliferator-activated receptor gamma-independent pathway.
pubmed:affiliation
Tulane University Heart & Vascular Institute, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural