Linked Life Data

9799653

Source:http://linkedlifedata.com/resource/pubmed/id/9799653

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1998-12-16
pubmed:abstractText
Phospholamban is a small phosphoprotein regulator of the Ca2+-pump of cardiac sarcoplasmic reticulum. Dephosphorylated phospholamban inhibits the Ca2+-pump and depresses contractility, whereas phosphorylation of phospholamban by cAMP-activated mechanisms relieves this inhibition and increases contractility. In order to better understand the function of phospholamban in living systems, a transgenic mouse model was established employing targeted overexpression of phospholamban to the atrium, which normally expresses low levels of the protein. Overexpression was achieved by fusing the alpha-MHC-promoter or the ANF-promoter to the phospholamban gene. Double transgenic mice were created by mating mice positive for each transgene. In single transgenic lineages, phospholamban was overexpressed four to six-fold in left atrium. In the double transgenic mice, phospholamban was overexpressed eight- to nine-fold. In the three transgenic strains. Ca2+ uptake by the sarcoplasmic reticulum was depressed to 22-30% of control values at low ionized calcium. This depression of Ca2+ uptake was largely reversed by addition of a phospholamban monoclonal antibody. In the atrial muscle strips, the time course of contraction was increased in a concentration-dependent manner by overexpression of phospholamban, whereas the basal developed tension was decreased up to 85% by phospholamban-overexpression. In all transgenic lineages, isoproterenol, a beta-adrenoceptor agonist, reversed the depression of contractility caused by overexpression of phospholamban and significantly shortened time parameters to levels approaching control values. These data demonstrate that overexpression of phospholamban in a mammalian myocardial tissue normally deficient in the protein substantially inhibits basal contractility, and furthermore suggest that in myocardial tissues containing high levels of the protein, phosphorylation of phospholamban can account for many of the positive inotropic and lusitropic effects of beta-adrenergic stimulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-2828
pubmed:author
pubmed:copyrightInfo
Copyright 1998 Academic Press
pubmed:issnType
Print
pubmed:volume
30
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1991-2002
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Targeted overexpression of phospholamban to mouse atrium depresses Ca2+ transport and contractility.
pubmed:affiliation
Institut für Pharmakologie und Toxikologie der Westfälischen Wilhelms-Universität, D-48129, Münster, Domagkstr. 12, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.