Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced DNA damage in vascular endothelial cells

Abstract

ObjectiveOmega-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 resultsWe 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reduced H2O2-induced senescence-associated β-galactosidase activity in the cells (by 31% and 22%, respectively), which was revoked by NRF2 silencing.ConclusionsOur results suggested that EPA and DHA attenuate oxidative stress-induced DNA damage in vascular endothelial cells through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.

Short‐term interleukin‐37 treatment improves vascular endothelial function, endurance exercise capacity, and whole‐body glucose metabolism in old mice

“…The ratio of L‐arginine to L‐citrulline tended to be higher in plasma from recIL‐37 vs. placebo‐treated mice, which also is consistent with greater NO synthesis. Moreover, we observed changes in metabolites that may reflect reduced inflammation and oxidative stress, including lower levels of cystine and kynurenine (González Esquivel et al, ) and higher levels of the cardioprotective free fatty acid DHA (Innes & Calder, ; Sakai et al, ). Indeed, supplementation with DHA, alone and in combination with eicosapentaenoic acid, improves NO‐mediated endothelial function in humans with CVD risk factors (Goodfellow, Bellamy, Ramsey, Jones, & Lewis, ; Mori et al, ; Rizza et al, ).…”

Potential neuroprotective and anti-inflammatory effects provided by omega-3 (DHA) against Zika virus infection in human SH-SY5Y cells

“…Therefore, molecules with the ability to modulate inflammation could be useful to inhibit ZIKV pathogenicity. It has been demonstrated that Docosahexaenoic acid (DHA, C22:6(omega-3)), a polyunsaturated fatty acid derived from omega-3 family, can inhibit NLRP3 inflammasome 16,17 and reduce intracellular reactive oxygen species 18 .…”

Reduced dietary omega-3 fatty acids intake is associated with sarcopenia in elderly patients with type 2 diabetes: a cross-sectional study of KAMOGAWA-DM cohort study

“…These activities were thought to occur by incorporating omega-3 fatty acids into myocyte membranes, which resulted in activating protein kinase C located upstream of mTOR and p70s6k. (38) Additionally, omega-3 fatty acids attenuate oxidative stress by suppressing forkhead boxcontaining protein, O1 (foxo1) pathway, (39) and suppressing foxo1 leads to suppression of muscle atrophy. (40) In summary, omega-3 fatty acids may stimulate protein synthesis.…”