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dc.contributor.authorKuosmanen, SM
dc.contributor.authorSihvola, V
dc.contributor.authorKansanen, E
dc.contributor.authorKaikkonen, MU
dc.contributor.authorLevonen, AL
dc.date.accessioned2018-08-14T12:19:19Z
dc.date.available2018-08-14T12:19:19Z
dc.date.issued2018
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/6797
dc.description.abstractOxidative stress predisposes to several aging-associated diseases, such as cardiovascular diseases and cancer. In aging, increase in the production of reactive oxygen species is typically accompanied with a decline in adaptive stress responses to oxidative stress. The decline is primarily due to a decrease in antioxidant production. Nuclear factor E2-Related Factor 2 (NRF2) is a key transcription factor regulating oxidative and electrophilic stress responses, but it has also been shown to play a role in the regulation of cell metabolism. NRF2 expression declines in aging, but the mechanisms remain unclear. In this study, we show that microRNAs (miRNAs) that are abundant in old endothelial cells decrease NRF2 expression by direct targeting of NRF2 mRNA. The effect is reversed by miRNA inhibition. The senescence-associated downregulation of NRF2 decreases endothelial glycolytic activity and stress tolerance both of which are restored after reinstating NRF2. Manipulation of the senescence-associated miRNA levels affects the glycolytic activity and stress tolerance consistently with the NRF2 results. We conclude that senescence-associated miRNAs are involved in the decline of NRF2 expression, thus contributing to the repression of adaptive responses during cell senescence.
dc.language.isoenglanti
dc.publisherElsevier BV
dc.relation.ispartofseriesRedox Biology
dc.relation.urihttp://dx.doi.org/10.1016/j.redox.2018.06.007
dc.rightsCC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectMicroRNA
dc.subjectaging
dc.subjectsenescence
dc.subjectNRF2
dc.subjectendothelial cell
dc.titleMicroRNAs mediate the senescence-associated decline of NRF2 in endothelial cells
dc.description.versionpublished version
dc.contributor.departmentA.I. Virtanen -instituutti
uef.solecris.id55844157en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© Authors
dc.relation.doi10.1016/j.redox.2018.06.007
dc.description.reviewstatuspeerReviewed
dc.format.pagerange77-83
dc.relation.issn2213-2317
dc.relation.volume18
dc.rights.accesslevelopenAccess
dc.type.okmA1
uef.solecris.openaccessOpen access -julkaisukanavassa ilmestynyt julkaisu


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