TY  - JOUR
AU  - Tinkov, Alexey
AU  - Nguyen, Thuy
AU  - Santamaria, Abe
AU  - Bowman, Aaron
AU  - Buha-Đorđević, Aleksandra
AU  - Paoliello, Monica Maria
AU  - Skalny, Anatoly
AU  - Aschner, Michael
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3910
AB  - Metal 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.
PB  - Springer
T2  - Archives of Toxicology
T1  - Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity
DO  - 10.1007/s00204-021-03048-6
ER  - 

@article{
author = "Tinkov, Alexey and Nguyen, Thuy and Santamaria, Abe and Bowman, Aaron and Buha-Đorđević, Aleksandra and Paoliello, Monica Maria and Skalny, Anatoly and Aschner, Michael",
year = "2021",
abstract = "Metal 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.",
publisher = "Springer",
journal = "Archives of Toxicology",
title = "Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity",
doi = "10.1007/s00204-021-03048-6"
}

Tinkov, A., Nguyen, T., Santamaria, A., Bowman, A., Buha-Đorđević, A., Paoliello, M. M., Skalny, A.,& Aschner, M.. (2021). Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity. in Archives of Toxicology
Springer..
https://doi.org/10.1007/s00204-021-03048-6

Tinkov A, Nguyen T, Santamaria A, Bowman A, Buha-Đorđević A, Paoliello MM, Skalny A, Aschner M. Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity. in Archives of Toxicology. 2021;.
doi:10.1007/s00204-021-03048-6 .

Tinkov, Alexey, Nguyen, Thuy, Santamaria, Abe, Bowman, Aaron, Buha-Đorđević, Aleksandra, Paoliello, Monica Maria, Skalny, Anatoly, Aschner, Michael, "Sirtuins as molecular targets, mediators, and protective agents in metal‑induced toxicity" in Archives of Toxicology (2021),
https://doi.org/10.1007/s00204-021-03048-6 . .