Linked Life Data

18294449

Source:http://linkedlifedata.com/resource/pubmed/id/18294449

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-3-17
pubmed:abstractText
RCAN1 (Adapt78) functions mainly, if not exclusively, as a regulator of calcineurin, a phosphatase that mediates many cellular responses to calcium. Identification of this regulatory activity has led to a surge of interest in RCAN1, since calcineurin is involved in many cellular and tissue functions, and its abnormal expression is associated with multiple pathologies. Recent studies have implicated RCAN1 as a regulator of angiogenesis. To more fully investigate the role of RCAN1 in vascular function, we first extended previous studies by assessing RCAN1 response in cultured endothelial cells to various vascular agonists. Strong induction of isoform 4 but not isoform 1 was observed in human umbilical vein- and bovine pulmonary aortic-endothelial cells in response to VEGF, thrombin, and ATP but not other agonists. Inductions were both calcium and calcineurin dependent, with the relative effect of each agonist cell-type dependent. Ectopic RCAN1 expression also inhibited calcineurin signaling in the HUVEC cells. Based on these strong RCAN1 responses and a lack of RCAN1-associated vascular studies beyond angiogenesis, we investigated the potential role of RCAN1 in vascular tone using whole mounted mesenteric artery. RCAN1 knockout mice exhibited an attenuated mesenteric vasoconstriction to phenylephrine as compared with wild-type. Overall contractility was unaffected, suggesting that this component of smooth muscle action is similar in the two mouse strains. Constriction in the knockout artery appeared to be potentiated by the addition of the nitric oxide synthase (NOS) inhibitor l-NAME, suggesting that elevated nitric oxide (NO) production occurs in the knockout vasculature and contributes to the weakened vasoconstriction. Our results reveal a newly identified vascular role for RCAN1, and a potential new target for treating vascular- and calcineurin-related disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1096-0384
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
472
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-50
pubmed:dateRevised
2008-5-6
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Regulation of vascular function by RCAN1 (ADAPT78).
pubmed:affiliation
Center for Cardiovascular Sciences, The Albany Medical College, Albany, NY 12208, USA.
pubmed:publicationType
Journal Article