Resveratrol blocks retrotransposition of LINE-1 through PPAR α and sirtuin-6.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 05 2022
11 05 2022
Historique:
received:
31
08
2021
accepted:
26
04
2022
entrez:
13
5
2022
pubmed:
14
5
2022
medline:
18
5
2022
Statut:
epublish
Résumé
The retroelement long interspersed element-1 (LINE-1 or L1) comprises about 17% of the human genome. L1 retrotransposition is known to cause genomic instability and related disorders, and resveratrol suppresses this retrotransposition; however, the underlying mechanism is still not elucidated. Recent observations showed that low-molecular-weight compounds might induce L1 retrotransposition through unknown mechanisms. This study aimed to determine polyphenol resveratrol (RV)'s effect on L1-RTP (retrotransposition) in somatic cells. Surprisingly, RV completely blocked L1-RTP. Experiments using the PPARα inhibitor GW6471 or siRNA-mediated PPARα depletion showed that RV-mediated L1-RTP's inhibition depended on peroxisome proliferator-activated receptor α (PPARα). We demonstrated that RV inhibits p38 and cAMP response element binding protein phosphorylation, which are involved in MAPK signaling, and the L1-ORF1 protein's chromatin recruitment. Furthermore, RV increased the expression of sirtuin-6 (SIRT6), which inhibited the activation of L1. The sirtuins family, SIRT1, SIRT6, and SIRT7, but not SIRT3, are involved in RV-mediated inhibition of L1-RTP. Overall, our findings suggest that RV directly modulates PPARα-mediated L1-RTP in somatic cells and that MAPK signaling interacts with SIRT6 closely and may play a role in preventing human diseases such as cancer.
Identifiants
pubmed: 35546166
doi: 10.1038/s41598-022-11761-0
pii: 10.1038/s41598-022-11761-0
pmc: PMC9095727
doi:
Substances chimiques
PPAR alpha
0
Retroelements
0
SIRT6 protein, human
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Sirtuins
EC 3.5.1.-
Resveratrol
Q369O8926L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7772Informations de copyright
© 2022. The Author(s).
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