Source:http://linkedlifedata.com/resource/pubmed/id/20228121
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2010-5-20
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pubmed:abstractText |
Ageing reduces the ability of cardiac myocytes to respond to inotropic agents. We hypothesized that hypoxia-inducible factor-1 (HIF-1) would improve the functional and Ca(2+) transient responses of ageing myocytes to the inotropic agents and this would act, in part, through altered mitochondrial activity. Young (3-4 months) and older Fischer 344 rats (18-20 months) were used. Hypoxia-inducible factor-1alpha was upregulated with ciclopirox olamine (CPX, 50 mg kg(1) on 2 days). Hypoxia-inducible factor-1 upregulation was detected by Western blot. Cardiomyocyte contraction and Ca(2+) transients were measured at baseline and after forskolin and ouabain. We also measured mitochondrial complex activities and production of reactive oxygen species (ROS). In the young group, forskolin (31%) and ouabain (31%) significantly increased percentage shortening. Similar changes were observed in the young + CPX group. Calcium transients also responded in a similar manner. However, in the older group, forskolin (12%) and ouabain (6%) did not significantly increase myocyte contractility or Ca(2+) transients. In the older + CPX group, the effects of forskolin (34%) and ouabain (29%) were restored. In the young + CPX group, there was increased ROS production and mitochondrial complex I and III activity compared with the young group. These differences were not observed in older groups. These data demonstrate an impaired functional and Ca(2+) effect of positive inotropic agents in older myocytes. Upregulation of HIF-1 restored this blunted response, but this was not related to changed mitochondrial activity induced by HIF-1. Thus, we found that HIF-1 improved inotropy in older myocytes without requiring mitochondrial activity changes.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Electron Transport Complex I,
http://linkedlifedata.com/resource/pubmed/chemical/Electron Transport Complex III,
http://linkedlifedata.com/resource/pubmed/chemical/Forskolin,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Ouabain,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridones,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/ciclopirox
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1469-445X
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
95
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
712-22
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pubmed:meshHeading |
pubmed-meshheading:20228121-Aging,
pubmed-meshheading:20228121-Animals,
pubmed-meshheading:20228121-Calcium,
pubmed-meshheading:20228121-Electron Transport Complex I,
pubmed-meshheading:20228121-Electron Transport Complex III,
pubmed-meshheading:20228121-Forskolin,
pubmed-meshheading:20228121-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:20228121-Mitochondria, Heart,
pubmed-meshheading:20228121-Myocardial Contraction,
pubmed-meshheading:20228121-Myocytes, Cardiac,
pubmed-meshheading:20228121-Ouabain,
pubmed-meshheading:20228121-Pyridones,
pubmed-meshheading:20228121-Rats,
pubmed-meshheading:20228121-Rats, Inbred F344,
pubmed-meshheading:20228121-Reactive Oxygen Species
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pubmed:year |
2010
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pubmed:articleTitle |
Hypoxia-inducible factor-1 improves inotropic responses of cardiac myocytes in ageing heart without affecting mitochondrial activity.
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pubmed:affiliation |
Department of Physiology and Biophysics, UMDNJ, Robert Wood Johnson Medical School, 675 Hoes Lane West, Piscataway, NJ 08854, USA.
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pubmed:publicationType |
Journal Article
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