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Curcumin induces multiple signaling pathways leading to vascular smooth muscle cell senescence

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dc.abstract.enCurcumin, a phytochemical present in the spice named turmeric, and one of the promising antiaging factors, is itself able to induce cellular senescence. We have recently shown that cells building the vasculature senesced as a result of curcumin treatment. Curcumin-induced senescence was DNA damageindependent; however, activation of ATM was observed. Moreover, neither increased ROS production, nor even ATM were indispensable for senescence progression. In this paper we tried to elucidate the mechanism of curcumin-induced senescence. We analyzed the time-dependence of the level and activity of numerous proteins involved in senescence progression in vascular smooth muscle cells and how inhibition p38 or p38 together with ATM, two proteins involved in canonical signaling pathways, influenced cell senescence. We showed that curcumin was able to influence many signaling pathways of which probably none was dominant and sufficient to induce senescence by itself. However, we cannot exclude that the switch between initiation and progression of senescence is the result of the impact of curcumin on signaling pathways engaging AMPK, ATM, sirtuin 1 and p300 and on their reciprocal interplay. Cytostatic concentration of curcumin induced cellular stress, which exceeded the adaptive response and, in consequence, led to cellular senescence, which is triggered by time dependent activation of several signaling pathways playing diverse roles in different phases of senescence progression. We also showed that activity of b-glucuronidase, the enzyme involved in deconjugation of the main metabolites of curcumin, glucuronides, increased in senescent cells. It suggests a possible local elevation of curcumin concentration in the organism.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorAchtabowska, Natalia
dc.contributor.authorBojko, Agnieszka
dc.contributor.authorSIKORA, EWA
dc.contributor.authorLitwinienko, Grzegorz
dc.contributor.authorMOSIENIAK, GRAŻYNA
dc.contributor.authorCzochara, Robert
dc.contributor.authorŻMIJEWSKA, ANNA BIELAK -
dc.contributor.authorGrabowska-Pyrzewicz, Wioleta
dc.date.accessioned2024-01-24T21:14:42Z
dc.date.available2024-01-24T21:14:42Z
dc.date.copyright2019-08-01
dc.date.issued2019
dc.description.accesstimeAT_PUBLICATION
dc.description.financeNie dotyczy
dc.description.versionFINAL_PUBLISHED
dc.description.volume20
dc.identifier.doi10.1007/S10522-019-09825-2
dc.identifier.issn1389-5729
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/104035
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofBiogerontology
dc.relation.pages783-798
dc.rightsCC-BY
dc.sciencecloudnosend
dc.subject.enCurcumin
dc.subject.enVSMCs
dc.subject.enSenescence
dc.subject.enATM
dc.subject.enAMPK
dc.subject.enb-glucuronidase
dc.titleCurcumin induces multiple signaling pathways leading to vascular smooth muscle cell senescence
dc.typeJournalArticle
dspace.entity.typePublication