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dc.creatorTinkov, Alexey
dc.creatorNguyen, Thuy
dc.creatorSantamaria, Abe
dc.creatorBowman, Aaron
dc.creatorBuha Đorđević, Aleksandra
dc.creatorPaoliello, Monica Maria
dc.creatorSkalny, Anatoly
dc.creatorAschner, Michael
dc.date.accessioned2021-06-10T12:23:01Z
dc.date.available2021-06-10T12:23:01Z
dc.date.issued2021
dc.identifier.issn0340-5761
dc.identifier.urihttps://farfar.pharmacy.bg.ac.rs/handle/123456789/3910
dc.description.abstractMetal dyshomeostasis, and especially overexposure, is known to cause adverse health effects due to modulation of a variety of metabolic pathways. An increasing body of literature has demonstrated that metal exposure may affect SIRT signaling, although the existing data are insufficient. Therefore, in this review we discuss the available data (PubMed-Medline, Google Scholar) on the influence of metal overload on sirtuin (SIRT) signaling and its association with other mechanisms involved in metal-induced toxicity. The existing data demonstrate that cadmium (Cd), mercury (Hg), arsenic (As), lead (Pb), aluminium (Al), hexavalent chromium (CrVI), manganese (Mn), iron (Fe), and copper (Cu) can inhibit SIRT1 activity. In addition, an inhibitory effect of Cd, Pb, As, and Fe on SIRT3 has been demonstrated. In turn, metal-induced inhibition of SIRT was shown to affect deacetylation of target proteins including FOXO, PGC1α, p53 and NF-kB. Increased acetylation downregulates PGC1α signaling pathway, resulting in cellular altered redox status and increased susceptibility to oxidative stress, as well as decreased mitochondrial biogenesis. Lower rates of LKB1 deacetylation may be responsible for metal-induced decreases in AMPK activity and subsequent metabolic disturbances. A shift to the acetylated FOXO results in increased expression of pro-apoptotic genes which upregulates apoptosis together with increased p53 signaling. Correspondingly, decreased NF-kB deacetylation results in upregulation of target genes of proinflammatory cytokines, enzymes, and cellular adhesion molecules thus promoting inflammation. Therefore, alterations in sirtuin activity may at least partially mediate metal-induced metabolic disturbances that have been implicated in neurotoxicity, nephrotoxicity, cardiotoxicity, and other toxic effects of heavy metals.
dc.publisherSpringer
dc.relationinfo:eu-repo/grantAgreement/ScienceFundRS/Promis/6066532/RS//
dc.relationMinistry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Centers “Digital biodesign and personalized healthcare” No075-15-2020-92
dc.relationGrants from the National Institute of Environmental Health Sciences (NIEHS)—R01ES10563 and NIEHS R01ES07331
dc.rightsrestrictedAccess
dc.sourceArchives of Toxicology
dc.subjectApoptosis
dc.subjectInflammation
dc.subjectMetals
dc.subjectAntioxidants
dc.subjectMitochondrial biogenesis
dc.subjectSirtuin
dc.titleSirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity
dc.typearticle
dc.rights.licenseARR
dcterms.abstractПаолиелло, Моница Мариа; Скалнy, Aнатолy; Тинков, Aлеxеy; Aсцхнер, Мицхаел; Нгуyен, Тхуy; Сантамариа, Aбе; Боwман, Aарон; Буха Ђорђевић, Aлександра;
dc.identifier.wos000653614200003
dc.identifier.doi10.1007/s00204-021-03048-6
dc.identifier.scopus2-s2.0-85106413049
dc.type.versionpublishedVersion


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