Linked Life Data

16585059

Source:http://linkedlifedata.com/resource/pubmed/id/16585059

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2006-5-5
pubmed:abstractText
Senescence is accompanied by oxidative stress and cardiac dysfunction, although the link between the two remains unclear. This study examined the role of antioxidant metallothionein on cardiomyocyte function, superoxide generation, the oxidative stress biomarker aconitase activity, cytochrome c release, and expression of oxidative stress-related proteins, such as the GTPase RhoA and NADPH oxidase protein p47phox in young (5-6 mo) and aged (26-28 mo) FVB wild-type (WT) and cardiac-specific metallothionein transgenic mice. Metallothionein mice showed a longer life span (by approximately 4 mo) than FVB mice evaluated by the Kaplan-Meier survival curve. Compared with young cardiomyocytes, aged myocytes displayed prolonged TR(90), reduced tolerance to high stimulus frequency, and slowed intracellular Ca2+ decay, all of which were nullified by metallothionein. Aging increased superoxide generation, active RhoA abundance, cytochrome c release, and p47phox expression and suppressed aconitase activity without affecting protein nitrotyrosine formation in the hearts. These aging-induced changes in oxidative stress and related protein biomarkers were attenuated by metallothionein. Aged metallothionein mouse myocytes were more resistant to the superoxide donor pyrogallol-induced superoxide generation and apoptosis. In addition, aging-associated prolongation in TR90 was blunted by the Rho kinase inhibitor Y-27632. Collectively, our data demonstrated that metallothionein may alleviate aging-induced cardiac contractile defects and oxidative stress, which may contribute to prolonged life span in metallothionein transgenic mice.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1024-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16585059-Aconitate Hydratase, pubmed-meshheading:16585059-Aging, pubmed-meshheading:16585059-Animals, pubmed-meshheading:16585059-Apoptosis, pubmed-meshheading:16585059-Calcium, pubmed-meshheading:16585059-Cytochromes c, pubmed-meshheading:16585059-Diastole, pubmed-meshheading:16585059-Gene Expression Regulation, pubmed-meshheading:16585059-Heart Ventricles, pubmed-meshheading:16585059-Metallothionein, pubmed-meshheading:16585059-Mice, pubmed-meshheading:16585059-Mice, Transgenic, pubmed-meshheading:16585059-Myocardial Contraction, pubmed-meshheading:16585059-Myocytes, Cardiac, pubmed-meshheading:16585059-Oxidative Stress, pubmed-meshheading:16585059-Pyrogallol, pubmed-meshheading:16585059-Superoxides, pubmed-meshheading:16585059-Tyrosine, pubmed-meshheading:16585059-rhoA GTP-Binding Protein
pubmed:year
2006
pubmed:articleTitle
Metallothionein prolongs survival and antagonizes senescence-associated cardiomyocyte diastolic dysfunction: role of oxidative stress.
pubmed:affiliation
Division of Pharmaceutical Sciences and Center for Cardiovascular Research and Alternative Medicine, University of Wyoming, Laramie, Wyoming 82071-3375, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural