Linked Life Data

9887981

Source:http://linkedlifedata.com/resource/pubmed/id/9887981

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1999-4-7
pubmed:abstractText
It is generally agreed that intracellular Ca2+ stores, the sarco(endo)plasmic-reticulum (SER), affect Ca2+ homeostasis and thus contractility of vascular smooth muscle. There is, however, no general consensus as to the magnitude of the SER contribution to Ca2+ handling, the basis for isoforms of the SER Ca(2+)-ATPases (SERCAs) or the role of an SER-associated regulatory protein, phospholamban (PLB). Although the biochemical and cell biological roles of the SER have been intensely studied in vitro, the development of gene-targeted and transgenic mouse models enables one to extend our information to the in vivo levels. A brief review of the role of PLB and SERCA function in vascular and endothelial cell function is presented. Studies on the PLB gene-ablated mouse indicate that vascular contractility is considerably altered. This is mirrored by changes in intracellular Ca2+. Moreover, differences in contractility of the gene-ablated tissues are eliminated by treatment with cyclopiazonic acid, which pharmacologically abolishes SER function by inhibiting the Ca(2+)-ATPase. Thus PLB modulation of sarcoplasmic reticulum (SR) Ca2+ uptake plays a major role in modulating vascular contractility. It is interesting that endothelium-dependent relaxation was decreased in the PLB-deficient aorta. This is surprising in light of the PLB distribution, thought to be limited to cardiac, slow skeletal and smooth muscle. Our data indicate the presence of PLB in endothelial cells and point to an unrecognized pathway for modulation of endothelial cell [Ca2+]i and vascular contractility. Data from smooth muscle tissues of the SERCA3 gene-ablated mouse demonstrate that this isoform affects endothelium-dependent function, but not that of smooth muscle, consistent with its known distribution. This isoform appears to perform a modulatory function, rather than the more essential role of SERCA2. Gene-targeted and transgenic models provide an important avenue for understanding the role of SER in vascular signalling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0001-6772
pubmed:author
pubmed:issnType
Print
pubmed:volume
164
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
589-97
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
The role of phospholamban and SERCA3 in regulation of smooth muscle-endothelial cell signalling mechanisms: evidence from gene-ablated mice.
pubmed:affiliation
Department of Molecular and Cellular Physiology, University of Cincinnati College of Medicine, OH 45267-0576, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review