Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-5-23
pubmed:abstractText
Altered regulation of signaling pathways can lead to pathologies including cardiac hypertrophy and heart failure. We report that neonatal and adult cardiomyocytes express chromogranin B (CGB), a Ca(2+) binding protein that modulates Ca(2+) release by the inositol 1,4,5-trisphosphate receptor (InsP(3)R). Using fluorescent Ca(2+) indicator dyes, we found that CGB regulates InsP(3)-dependent Ca(2+) release in response to angiotensin II, an octapeptide hormone that promotes cardiac hypertrophy. ELISA experiments and luciferase reporter assays identified angiotensin II as a potent inducer of brain natriuretic peptide (BNP), a hormone that recently emerged as an important biomarker in cardiovascular disease. CGB was found to regulate angiotensin II-stimulated and basal secretion, expression and promoter activity of BNP that depend on the InsP(3)R. Moreover, we provide evidence that CGB acts via the transcription activity of nuclear factor kappaB in an InsP(3)/Ca(2+)-dependent manner but independent of nuclear factor of activated T cells. In vivo experiments further showed that cardiac hypertrophy induced by angiotensin II, a condition characterized by increased ventricular BNP production, is associated with upregulation of ventricular CGB expression. Overexpression of CGB in cardiomyocytes, in turn, induced the BNP promoter. The evidence presented in this study identifies CGB as a novel regulator of cardiomyocyte InsP(3)/Ca(2+)-dependent signaling, nuclear factor kappaB activity, and BNP production.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
23
pubmed:volume
102
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1230-8
pubmed:dateRevised
2011-3-16
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Chromogranin B regulates calcium signaling, nuclear factor kappaB activity, and brain natriuretic peptide production in cardiomyocytes.
pubmed:affiliation
Department of Pharmacology, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520-8066, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural