Linked Life Data

18729805

Source:http://linkedlifedata.com/resource/pubmed/id/18729805

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2008-8-27
pubmed:abstractText
Circulating insulin-like growth factor-1 (IGF-1) levels are linked to cardiac performance and lifespan. However, the role of IGF-1 levels in aging-associated cardiac dysfunction has not been defined. This study was designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on aging-induced cardiomyocyte contractile and intracellular Ca(++) dysfunction. Cardiomyocytes were isolated from young (2- to 4-month-old) and old (24- to 26-month-old) male C57BL/6 and LID mice. Cardiomyocyte contractile and intracellular Ca(++) transient properties were evaluated, including peak shortening (PS), maximal velocity of shortening/relengthening (+/-dL/dt), time-to-PS (TPS), time-to-90% relengthening (TR(90)), electrically stimulated change in fura-fluorescence intensity (DeltaFFI), and intracellular Ca(++) decay rate. Aged C57BL/6 myocytes displayed reduced PS, +/-dL/dt and DeltaFFI as well as prolonged TR(90) and intracellular Ca(++) decay. IGF-1 deficiency decreased +/-dL/dt, and prolonged TR(90) with little change in other mechanical indices. Interestingly, LID dampened aging-induced changes in cardiomyocyte function. Aging and IGF-1 deficiency both contributed to whole-body glucose intolerance. Aging downregulated expression of Akt, Klotho, and pAMPK, whereas it upregulated p53 expression, the effects of which were cancelled by IGF-1 deficiency. Aging and IGF-1 deficiency significantly reduced expression of the transcriptional factor Foxo3a without an overt effect on the mammalian target of rapamycin (mTOR) level. Collectively, these data depicted that IGF-1 deficiency may reduce the cardiomyocyte sensitivity to aging-induced mechanical dysfunction. Our data suggest that regulation of Akt, p53, adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, and Klotho may play a role, at least in part, in IGF-1 deficiency-induced "desensitization" of cardiac aging.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1549-1684
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
725-33
pubmed:dateRevised
2011-3-1
pubmed:meshHeading
pubmed-meshheading:18729805-AMP-Activated Protein Kinases, pubmed-meshheading:18729805-Aging, pubmed-meshheading:18729805-Animals, pubmed-meshheading:18729805-Calcium Signaling, pubmed-meshheading:18729805-Cardiomyopathies, pubmed-meshheading:18729805-Genetic Predisposition to Disease, pubmed-meshheading:18729805-Glucose Tolerance Test, pubmed-meshheading:18729805-Glucuronidase, pubmed-meshheading:18729805-Heart Ventricles, pubmed-meshheading:18729805-Insulin-Like Growth Factor I, pubmed-meshheading:18729805-Liver, pubmed-meshheading:18729805-Mice, pubmed-meshheading:18729805-Mice, Inbred C57BL, pubmed-meshheading:18729805-Mice, Transgenic, pubmed-meshheading:18729805-Multienzyme Complexes, pubmed-meshheading:18729805-Myocardial Contraction, pubmed-meshheading:18729805-Myocytes, Cardiac, pubmed-meshheading:18729805-Oncogene Protein v-akt, pubmed-meshheading:18729805-Organ Specificity, pubmed-meshheading:18729805-Protein-Serine-Threonine Kinases, pubmed-meshheading:18729805-Tumor Suppressor Protein p53
pubmed:year
2008
pubmed:articleTitle
Deficiency of insulin-like growth factor 1 reduces sensitivity to aging-associated cardiomyocyte dysfunction.
pubmed:affiliation
Division of Pharmaceutical Sciences & Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, WY 82071, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural