Resveratrol blocks retrotransposition of LINE-1 through PPAR α and sirtuin-6
Open accessAbstract
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.
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Resveratrol increases SIRT6.
“Resveratrol has been reported to increase SIRT6 (Okudaira et al. 2022).”
From Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging (2023) · cites this paper as Okudaira et al. 2022
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
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- Authors
- Okudaira, N., Ishizaka, Y., & Tamamori-Adachi, M.
- Affiliations
- Teikyo University (JP)
- National Center for Global Health and Medicine (JP)
- Corresponding author
- Okudaira, Noriyuki
- ORCID
- Ishizaka, Yukihito
- Venue
- Scientific Reports
- Published
- 2022-05-11
- Volume
- 12
- Issue
- 1
- Pages
- 7772-7772
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC9095727
- OpenAlex
- W4280492450
- Cited by
- 18
- References
- 53
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 5 · 2023: 2 · 2022: 1
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science KAKENHI (20K05943)
- Topics
- Health Sciences › Medicine › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- resveratrol, LINE-1 retrotransposition, retrotransposons, PPARα, SIRT6, MAPK signaling, p38 phosphorylation, CREB phosphorylation, ORF1 protein, chromatin recruitment, somatic cells, genomic instability, polyphenols
- MeSH terms
- Resveratrol, Humans, Retroelements, Long Interspersed Nucleotide Elements, Sirtuins, PPAR alpha, Sirtuin 1
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