Linked Life Data

14613911

Source:http://linkedlifedata.com/resource/pubmed/id/14613911

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-11-17
pubmed:abstractText
Type 1 protein phosphatase (PP1) is a negative regulator of cardiac function. However, studies on the status and regulation of sarcoplasmic reticulum (SR)-associated PP1 activity in failing hearts are limited. We studied PP1 activity and protein and mRNA expression of the catalytic subunit of PP1 (PP1C) and protein levels of PP1-specific inhibitors [inhibitor 1 (Inh-1) and inhibitor 2 (Inh-2)] in the left ventricular (LV) myocardium of 6 dogs with heart failure (HF; LV ejection fraction, 23 +/- 2%) and 6 normal dogs. In failing LV tissue, PP1 activity values (expressed as pmol 32P. min-1. mg of noncollagen protein-1) in the homogenate, crude membranes, cytosol, and purified SR were increased by 52, 54, 55, and 72%, respectively. Trypsin treatment released PP1 but not type 2A protein phosphatase from the SR. In the supernatant of trypsin-treated SR, PP1 activity was approximately 24% higher in failing hearts than in normal control hearts. A similar increase in protein expression of PP1C was observed in the nontrypsinized SR. Heat-denatured phosphorylated SR inhibited PP1 activity by 30%, which suggests the presence of Inh-1 or -2 or both in the SR. With the use of a specific antibody, both Inh-1 and -2 proteins were found in the SR; the former was decreased by 56% in the failing SR, whereas the latter did not change. These results suggest that protein phosphatase activity bound to the SR is increased and is predominantly type 1. Increased SR-associated PP1 activity in failing hearts appears to be due partly to increased expression of PP1C and partly to reduced levels of Inh-1 but not Inh-2 protein. Thus inhibition of PP1 activity in the SR appears to be a potential therapeutic target for improving LV function in failing hearts, because it may lead to increased SR Ca2+ uptake, which is impaired in failing hearts.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
285
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2373-81
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:14613911-Animals, pubmed-meshheading:14613911-Blood Pressure, pubmed-meshheading:14613911-Calcium-Transporting ATPases, pubmed-meshheading:14613911-Carrier Proteins, pubmed-meshheading:14613911-Dogs, pubmed-meshheading:14613911-Female, pubmed-meshheading:14613911-Gene Expression Regulation, Enzymologic, pubmed-meshheading:14613911-Heart Failure, pubmed-meshheading:14613911-Heart Rate, pubmed-meshheading:14613911-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:14613911-Male, pubmed-meshheading:14613911-Myocardium, pubmed-meshheading:14613911-Phosphoprotein Phosphatases, pubmed-meshheading:14613911-Protein Phosphatase 1, pubmed-meshheading:14613911-Proteins, pubmed-meshheading:14613911-Sarcoplasmic Reticulum, pubmed-meshheading:14613911-Sarcoplasmic Reticulum Calcium-Transporting ATPases, pubmed-meshheading:14613911-Ventricular Dysfunction, Left
pubmed:year
2003
pubmed:articleTitle
Cardiac SR-coupled PP1 activity and expression are increased and inhibitor 1 protein expression is decreased in failing hearts.
pubmed:affiliation
Division of Cardiovascular Medicine, Department of Medicine, Henry Ford Heart and Vascular Institute, Detroit, MI 48202, USA. rgupta1@hfhs.org
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.