Linked Life Data

21421818

Source:http://linkedlifedata.com/resource/pubmed/id/21421818

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2011-6-2
pubmed:abstractText
Mice with three amino acid mutations in the calmodulin binding domain of type-2 ryanodine receptor ion channel (Ryr2(ADA/ADA) mice) have impaired intracellular Ca(2+) handling and cardiac hypertrophy with death at an early age. In this report, the role of signaling molecules implicated in cardiac hypertrophy of Ryr2(ADA/ADA) mice was investigated. Calcineurin A-? (CNA-?) and nuclear factor of activated T cell (NFAT) signaling were monitored in mice carrying either luciferase transgene driven by NFAT-dependent promoter or knockout of CNA-?. NFAT transcriptional activity in Ryr2(ADA/ADA) hearts was not markedly upregulated at embryonic day 16.5 compared with wild-type but significantly increased at postnatal days 1 and 10. Ablation of CNA-? extended the life span of Ryr2(ADA/ADA) mice and enhanced cardiac function without improving sarcoplasmic reticulum Ca(2+) handling or suppressing the expression of genes implicated in cardiac hypertrophy. Embryonic day 16.5 Ryr2(ADA/ADA) mice had normal heart weights with no major changes in Akt1 and class II histone deacetylase phosphorylation and myocyte enhancer factor-2 activity. In contrast, phosphorylation levels of Erk1/2, p90 ribosomal S6 kinases (p90RSKs), and GSK-3? were increased in hearts of embryonic day 16.5 homozygous mutant mice. The results indicate that an impaired calmodulin regulation of RyR2 was neither associated with an altered CNA-?/NFAT, class II histone deacetylase (HDAC)/MEF2, nor Akt signaling in embryonic day 16.5 hearts; rather increased Erk1/2 and p90RSK phosphorylation levels likely leading to reduced GSK-3? activity were found to precede development of cardiac hypertrophy in mice expressing dysfunctional ryanodine receptor ion channel.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1522-1539
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H2187-95
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:21421818-Animals, pubmed-meshheading:21421818-Calcineurin, pubmed-meshheading:21421818-Cardiomegaly, pubmed-meshheading:21421818-Extracellular Signal-Regulated MAP Kinases, pubmed-meshheading:21421818-Female, pubmed-meshheading:21421818-Glycogen Synthase Kinase 3, pubmed-meshheading:21421818-Heart, pubmed-meshheading:21421818-Male, pubmed-meshheading:21421818-Mice, pubmed-meshheading:21421818-Mice, Knockout, pubmed-meshheading:21421818-Mice, Transgenic, pubmed-meshheading:21421818-Models, Animal, pubmed-meshheading:21421818-NFATC Transcription Factors, pubmed-meshheading:21421818-Proto-Oncogene Proteins c-akt, pubmed-meshheading:21421818-Ribosomal Protein S6 Kinases, 90-kDa, pubmed-meshheading:21421818-Ryanodine Receptor Calcium Release Channel, pubmed-meshheading:21421818-Signal Transduction
pubmed:year
2011
pubmed:articleTitle
Dysfunctional ryanodine receptor and cardiac hypertrophy: role of signaling molecules.
pubmed:affiliation
Dept. of Biochemistry and Biophysics, Univ. of North Carolina, Chapel Hill, NC 27599-7260, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural