Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells
Sakai C, Ishida M, Ohba H, Yamashita H, Uchida H, Yoshizumi M, Ishida T
PloS one · 128 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- University or hospital
- Tokyo Medical and Dental University
- Government
- Japan Society for the Promotion of Science
- Government
- Grants in Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (KAKENHI)
- Grants
- Japan Society for the Promotion of Science (17K10449); Japan Society for the Promotion of Science (15K09122); Japan Society for the Promotion of Science (22590528); Japan Society for the Promotion of Science (26461852)
Based on 3 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2017-11-09 · PLoS One · vol. 12 · issue 11 · p. e0187934
- Publisher
- Public Library of Science
- Cited
- 180 citations · more than 99% of similar papers · 9.3× the field average
- Impact
- Top 10% most cited in its field
- References
- 43 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Fatty Acid Research and Health · Antioxidant Activity and Oxidative Stress · Edible Oils Quality and Analysis
- Keywords
- DNA damage, Oxidative stress, Reactive oxygen species, Docosahexaenoic acid, Eicosapentaenoic acid, Superoxide dismutase, Antioxidant, Biochemistry, Heme oxygenase, Fish oil, Biology, Polyunsaturated fatty acid, Chemistry, Fatty acid, Heme, DNA, Enzyme
- MeSH
- cell line, endothelial cells, humans, dna damage, hydrogen peroxide, reactive oxygen species, superoxide dismutase, fatty acids, omega-3, fish oils, gene expression regulation, oxidative stress, heme oxygenase-1, thioredoxin reductase 1, cellular senescence
7 authors
From JP
- Chiemi SakaiHiroshima University
- Mari Ishida · correspondingHiroshima University
- Hideo OhbaHiroshima University
- Hiromitsu YamashitaHiroshima University
- Hitomi UchidaHiroshima University
- Masao YoshizumiHiroshima University
Abstract
Objective
Omega-3 fatty acids, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), likely prevent cardiovascular disease, however their mechanisms remain unclear. Recently, the role of DNA damage in atherogenesis has been receiving considerable attention. Here, we investigated the effects of EPA and DHA on DNA damage in vascular endothelial cells to clarify their antiatherogenic mechanisms.
Methods and results
We determined the effect of EPA and DHA on H2O2-induced DNA damage response in human aortic endothelial cells. Immunofluorescence staining showed that γ-H2AX foci formation, a prominent marker of DNA damage, was significantly reduced in the cells treated with EPA and DHA (by 47% and 48%, respectively). H2O2-induced activation of ATM, a major kinase orchestrating DNA damage response, was significantly reduced with EPA and DHA treatment (by 31% and 33%, respectively). These results indicated EPA and DHA attenuated DNA damage independently of the DNA damage response. Thus the effects of EPA and DHA on a source of DNA damage were examined. EPA and DHA significantly reduced intracellular reactive oxygen species under both basal condition and H2O2 stimulation. In addition, the mRNA levels of antioxidant molecules, such as heme oxygenase-1, thioredoxin reductase 1, ferritin light chain, ferritin heavy chain and manganese superoxide dismutase, were significantly increased with EPA and DHA. Silencing nuclear factor erythroid 2-related factor 2 (NRF2) remarkably abrogated the increases in mRNA levels of antioxidant molecules and the decrease in intracellular reactive oxygen species. Furthermore, EPA and DHA significantly reduced H2O2-induced senescence-associated β-galactosidase activity in the cells (by 31% and 22%, respectively), which was revoked by NRF2 silencing.
Conclusions
Our results suggested that EPA and DHA attenuate oxidative stress-induced DNA damage in vascular endothelial cells through upregulation of NRF2-mediated antioxidant response. Therefore omega-3 fatty acids likely help prevent cardiovascular disease, at least in part, by their genome protective properties.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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