PMID- 29121093
OWN - NLM
STAT- MEDLINE
DCOM- 20171211
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 11
DP  - 2017
TI  - Fish oil omega-3 polyunsaturated fatty acids attenuate oxidative stress-induced 
      DNA damage in vascular endothelial cells.
PG  - e0187934
LID - 10.1371/journal.pone.0187934 [doi]
LID - e0187934
AB  - 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 gamma-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 beta-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      (by 31% and 22%, respectively), which was revoked by NRF2 silencing.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.
FAU - Sakai, Chiemi
AU  - Sakai C
AD  - Department of Cardiovascular Physiology and Medicine, Graduate School of 
      Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Ishida, Mari
AU  - Ishida M
AUID- ORCID: 0000-0003-0881-0182
AD  - Department of Cardiovascular Physiology and Medicine, Graduate School of 
      Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Ohba, Hideo
AU  - Ohba H
AD  - Department of Cardiovascular Physiology and Medicine, Graduate School of 
      Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Yamashita, Hiromitsu
AU  - Yamashita H
AD  - Department of Cardiovascular Physiology and Medicine, Graduate School of 
      Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Uchida, Hitomi
AU  - Uchida H
AD  - Department of Cardiovascular Physiology and Medicine, Graduate School of 
      Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Yoshizumi, Masao
AU  - Yoshizumi M
AD  - Department of Cardiovascular Physiology and Medicine, Graduate School of 
      Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
FAU - Ishida, Takafumi
AU  - Ishida T
AD  - Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, 
      Japan.
LA  - eng
PT  - Journal Article
DEP - 20171109
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Fatty Acids, Omega-3)
RN  - 0 (Fish Oils)
RN  - 0 (Reactive Oxygen Species)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.8.1.9 (TXNRD1 protein, human)
RN  - EC 1.8.1.9 (Thioredoxin Reductase 1)
SB  - IM
MH  - Cell Line
MH  - Cellular Senescence/drug effects
MH  - DNA Damage
MH  - Endothelial Cells/cytology/*drug effects/metabolism
MH  - Fatty Acids, Omega-3/*pharmacology
MH  - Fish Oils/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Heme Oxygenase-1/genetics
MH  - Humans
MH  - Hydrogen Peroxide/*adverse effects
MH  - Oxidative Stress/*drug effects
MH  - Reactive Oxygen Species/metabolism
MH  - Superoxide Dismutase/genetics
MH  - Thioredoxin Reductase 1/genetics
PMC - PMC5679535
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/11/10 06:00
MHDA- 2017/12/12 06:00
PMCR- 2017/11/09
CRDT- 2017/11/10 06:00
PHST- 2017/08/11 00:00 [received]
PHST- 2017/10/27 00:00 [accepted]
PHST- 2017/11/10 06:00 [entrez]
PHST- 2017/11/10 06:00 [pubmed]
PHST- 2017/12/12 06:00 [medline]
PHST- 2017/11/09 00:00 [pmc-release]
AID - PONE-D-17-29844 [pii]
AID - 10.1371/journal.pone.0187934 [doi]
PST - epublish
SO  - PLoS One. 2017 Nov 9;12(11):e0187934. doi: 10.1371/journal.pone.0187934. 
      eCollection 2017.