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Article: Linkage of cardiac gene expression profiles and ETS2 with lifespan variability in rats

TitleLinkage of cardiac gene expression profiles and ETS2 with lifespan variability in rats
Authors
Issue Date2012
Citation
Aging Cell, 2012, v. 11 n. 2, p. 350-359 How to Cite?
AbstractLongevity variability is a common feature of aging in mammals, but the mechanisms responsible for this remain largely unknown. Using microarray datasets coupled with prediction analysis of microarrays (PAM), we identified a set of 252 cardiac transcripts predictive of relative lifespan in Wistar and Fisher 344 rats. Prediction analysis of microarrays 'tests' of rat heart transcriptomes from a third longer lived Fisher×Norway Brown rat strain validated the predictive value of this gene subset. The expression patterns of these genes were highly conserved, and corresponding promoter regions were employed to identify common cis-elements and trans-activating factors implicated in their control. Specifically, four transcription factors (Max, Ets2, Erg, and Msx2) present in heart displayed longevity-dependent, strain-independent changes in abundance, but only ETS2 had an expression profile that directly correlated with the relative lifespan gene set. In heart, ETS2 was prevalent in cardiomyocytes (CMs) and showed a high degree of myocyte-to-myocyte variability predominantly in adult rat hearts prior to the exponential increase in the rate of mortality. Exclusively in this group, elevated ETS2 significantly overlapped with TUNEL staining in heart myocytes. In response to sympathetic stimuli, ETS2 is also up-regulated, and functionally, adenovirus-mediated over-expression of ETS2 promotes apoptosis-inducing factor-mediated, caspase-independent programmed necrosis exclusively in CMs that can be fully inhibited by the PARP-1 inhibitor DPQ. We conclude that variations in ETS2 abundance in hearts of adult rodents and the associated loss of CMs contribute at least partially, to the longevity variability observed during normal aging of rats through activation of programmed necrosis. © 2012.
Persistent Identifierhttp://hdl.handle.net/10722/195135
ISSN
2015 Impact Factor: 5.76
2015 SCImago Journal Rankings: 4.374
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorSheydina, A-
dc.contributor.authorVolkova, M-
dc.contributor.authorJiang, L-
dc.contributor.authorJuhasz, O-
dc.contributor.authorZhang, J-
dc.contributor.authorTae, H-J-
dc.contributor.authorPerino, MG-
dc.contributor.authorWang, M-
dc.contributor.authorZhu, Y-
dc.contributor.authorLakatta, EG-
dc.contributor.authorBoheler, KR-
dc.date.accessioned2014-02-25T01:40:13Z-
dc.date.available2014-02-25T01:40:13Z-
dc.date.issued2012-
dc.identifier.citationAging Cell, 2012, v. 11 n. 2, p. 350-359-
dc.identifier.issn1474-9718-
dc.identifier.urihttp://hdl.handle.net/10722/195135-
dc.description.abstractLongevity variability is a common feature of aging in mammals, but the mechanisms responsible for this remain largely unknown. Using microarray datasets coupled with prediction analysis of microarrays (PAM), we identified a set of 252 cardiac transcripts predictive of relative lifespan in Wistar and Fisher 344 rats. Prediction analysis of microarrays 'tests' of rat heart transcriptomes from a third longer lived Fisher×Norway Brown rat strain validated the predictive value of this gene subset. The expression patterns of these genes were highly conserved, and corresponding promoter regions were employed to identify common cis-elements and trans-activating factors implicated in their control. Specifically, four transcription factors (Max, Ets2, Erg, and Msx2) present in heart displayed longevity-dependent, strain-independent changes in abundance, but only ETS2 had an expression profile that directly correlated with the relative lifespan gene set. In heart, ETS2 was prevalent in cardiomyocytes (CMs) and showed a high degree of myocyte-to-myocyte variability predominantly in adult rat hearts prior to the exponential increase in the rate of mortality. Exclusively in this group, elevated ETS2 significantly overlapped with TUNEL staining in heart myocytes. In response to sympathetic stimuli, ETS2 is also up-regulated, and functionally, adenovirus-mediated over-expression of ETS2 promotes apoptosis-inducing factor-mediated, caspase-independent programmed necrosis exclusively in CMs that can be fully inhibited by the PARP-1 inhibitor DPQ. We conclude that variations in ETS2 abundance in hearts of adult rodents and the associated loss of CMs contribute at least partially, to the longevity variability observed during normal aging of rats through activation of programmed necrosis. © 2012.-
dc.languageeng-
dc.relation.ispartofAging Cell-
dc.titleLinkage of cardiac gene expression profiles and ETS2 with lifespan variability in rats-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1111/j.1474-9726.2012.00794.x-
dc.identifier.pmid22247964-
dc.identifier.scopuseid_2-s2.0-84862800671-
dc.identifier.volume11-
dc.identifier.issue2-
dc.identifier.spage350-
dc.identifier.epage359-
dc.identifier.isiWOS:000301523000021-

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