Linked Life Data

18759454

Source:http://linkedlifedata.com/resource/pubmed/id/18759454

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
38
pubmed:dateCreated
2008-9-16
pubmed:abstractText
Atrial natriuretic peptide (ANP) is an endogenous peptide hormone that is synthesized and secreted by the myocardium in health and disease. Although the bioactivity of this molecule has been studied extensively, cellular mechanisms governing its processing and secretion are not fully understood. Through a yeast two-hybrid screen of a cDNA library made from tissue of a failing human heart, we have discovered that the precursor of ANP, natriuretic peptide precursor (NPPA), physically interacts with the N-terminus of apoptosis signal-regulating kinase 1 (ASK1), a kinase believed to be involved in the pathogenesis of heart failure. We demonstrated that NPPA is a substrate of ASK1 in an in vitro kinase assay. Indirect immunofluorescence microscopy shows that, when expressed in Hela cells, ASK1 and NPPA exhibit distinct, but overlapping, staining patterns, suggesting partial colocalization in cells. Additionally, coexpressing wild-type ASK1 with NPPA in Hela cells led to reduced levels of NPPA in the culture medium, suggesting that ASK1 negatively impacts NPPA processing and/or secretion. This negative effect was less pronounced when a dominant-negative allele of ASK1 with deficient kinase activity was coexpressed with NPPA. Because both ASK1 and ANP are associated with pathologic cardiac hypertrophy, their interaction may have pathophysiological and therapeutic relevance.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10041-8
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Apoptosis signal-regulating kinase 1 attenuates atrial natriuretic peptide secretion.
pubmed:affiliation
Cardiovascular Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't