Linked Life Data

21412239

Source:http://linkedlifedata.com/resource/pubmed/id/21412239

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-6-6
pubmed:abstractText
Apelin and its G-protein-coupled receptor APJ are potent regulators of the cardiovascular system. Recent studies have suggested that apelin-APJ reverses the function of angiotensin II (Ang II)-the Ang II type 1 receptor (AT(1)). However, the mechanism remains unclear because of the accumulating evidences that apelin-APJ may contribute to both cardioprotection and pathological progression. In human embryonic kidney 293 cells, we found that coexpression with APJ significantly suppressed the phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) induced by Ang II-AT(1), whereas apelin abolished this attenuation through activated APJ independently of its heterodimerization. Pretreatment with the Gi/o-specific inhibitor pertussis toxin (PTX) restituted the ERK1/2 phosphorylation level similar to that found with AT(1) and APJ coexpression without apelin stimulation. In contrast, coexpression of the beta-2-adrenergic receptor or the pharmacologically non-activated Ang II type 2 receptor (AT(2)) pretreated with the AT(2)-specific antagonist, PD123319, did not affect ERK1/2 phosphorylation through AT(1). Pretreatment with 30?nM of the AT(1) blocker (ARB) TA-606A suppressed 50% of the AT(1)-mediated ERK1/2 phosphorylation, whereas 30?nM of TA-606A achieved 75% suppression when the non-activated APJ was coexpressed without ligand or PTX. However, 120?nM of TA-606A failed to reach the target phosphorylation when it was coexpressed with activated APJ with apelin. Based on these results, we demonstrated that non-activated APJ may suppress Ang II-AT(1) signaling, whereas this ligand-independent function was diminished with apelin activation. These results may be relevant to the potential contribution of apelin-APJ to ARB treatment in the clinical realm.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1348-4214
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
701-6
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Non-activated APJ suppresses the angiotensin II type 1 receptor, whereas apelin-activated APJ acts conversely.
pubmed:affiliation
Department of Cardiovascular Surgery, Saitama Medical Center, Saitama, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural