PMID- 21130106
OWN - NLM
STAT- MEDLINE
DCOM- 20110224
LR  - 20211020
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Print)
IS  - 0041-008X (Linking)
VI  - 251
IP  - 1
DP  - 2011 Feb 15
TI  - Omega-3 fatty acid oxidation products prevent vascular endothelial cell 
      activation by coplanar polychlorinated biphenyls.
PG  - 41-9
LID - 10.1016/j.taap.2010.11.013 [doi]
AB  - Coplanar polychlorinated biphenyls (PCBs) may facilitate development of 
      atherosclerosis by stimulating pro-inflammatory pathways in the vascular 
      endothelium. Nutrition, including fish oil-derived long-chain omega-3 fatty 
      acids, such as docosahexaenoic acid (DHA, 22:6omega-3), can reduce inflammation and 
      thus the risk of atherosclerosis. We tested the hypothesis that cyclopentenone 
      metabolites produced by oxidation of DHA can protect against PCB-induced 
      endothelial cell dysfunction. Oxidized DHA (oxDHA) was prepared by incubation of 
      the fatty acid with the free radical generator 2,2-azo-bis(2-amidinopropane) 
      dihydrochloride (AAPH). Cellular pretreatment with oxDHA prevented production of 
      superoxide induced by PCB77, and subsequent activation of nuclear factor-kappaB 
      (NF-kappaB). A(4)/J(4)-neuroprostanes (NPs) were identified and quantitated using HPLC 
      ESI tandem mass spectrometry. Levels of these NPs were markedly increased after 
      DHA oxidation with AAPH. The protective actions of oxDHA were reversed by 
      treatment with sodium borohydride (NaBH(4)), which concurrently abrogated A(4)/J(4)-NP 
      formation. Up-regulation of monocyte chemoattractant protein-1 (MCP-1) by PCB77 
      was markedly reduced by oxDHA, but not by un-oxidized DHA. These protective 
      effects were proportional to the abundance of A(4)/J(4) NPs in the oxidized DHA 
      sample. Treatment of cells with oxidized eicosapentaenoic acid (EPA, 20:5omega-3) 
      also reduced MCP-1 expression, but less than oxDHA. Treatment with DHA-derived 
      cyclopentenones also increased DNA binding of NF-E2-related factor-2 (Nrf2) and 
      downstream expression of NAD(P)H:quinone oxidoreductase (NQO1), similarly to the 
      Nrf-2 activator sulforaphane. Furthermore, sulforaphane prevented PCB77-induced 
      MCP-1 expression, suggesting that activation of Nrf-2 mediates the observed 
      protection against PCB77 toxicity. Our data implicate A(4)/J(4)-NPs as mediators of 
      omega-3 fatty acid-mediated protection against the endothelial toxicity of 
      coplanar PCBs.
CI  - (c) 2010 Elsevier Inc. All rights reserved.
FAU - Majkova, Zuzana
AU  - Majkova Z
AD  - Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536-0200, 
      USA.
FAU - Layne, Joseph
AU  - Layne J
FAU - Sunkara, Manjula
AU  - Sunkara M
FAU - Morris, Andrew J
AU  - Morris AJ
FAU - Toborek, Michal
AU  - Toborek M
FAU - Hennig, Bernhard
AU  - Hennig B
LA  - eng
GR  - GM50388/GM/NIGMS NIH HHS/United States
GR  - P20 RR021954-03/RR/NCRR NIH HHS/United States
GR  - P42 ES007380/ES/NIEHS NIH HHS/United States
GR  - S10 RR024598/RR/NCRR NIH HHS/United States
GR  - R01 GM050388/GM/NIGMS NIH HHS/United States
GR  - P42 ES007380-14/ES/NIEHS NIH HHS/United States
GR  - P20RR021954/RR/NCRR NIH HHS/United States
GR  - P42ES007380/ES/NIEHS NIH HHS/United States
GR  - P20 RR021954/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101201
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (Antioxidants)
RN  - 0 (Borohydrides)
RN  - 0 (Cyclopentanes)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprostanes)
RN  - 11062-77-4 (Superoxides)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 87L0B9CPPA (sodium borohydride)
RN  - AAN7QOV9EA (Eicosapentaenoic Acid)
RN  - DFC2HB4I0K (Polychlorinated Biphenyls)
RN  - EC 1.6.5.2 (NAD(P)H Dehydrogenase (Quinone))
RN  - Q0U2IGF9CK (cyclopentenone)
RN  - Y2I6546TMI (3,4,3',4'-tetrachlorobiphenyl)
SB  - IM
MH  - Animals
MH  - Antioxidants/metabolism
MH  - Borohydrides/pharmacology
MH  - Cells, Cultured
MH  - Cyclopentanes/metabolism
MH  - Cytoprotection
MH  - Docosahexaenoic Acids/*metabolism
MH  - Eicosapentaenoic Acid/*metabolism
MH  - Endothelial Cells/*drug effects/metabolism
MH  - NAD(P)H Dehydrogenase (Quinone)/metabolism
MH  - NF-E2-Related Factor 2/metabolism
MH  - NF-kappa B/metabolism
MH  - Neuroprostanes/metabolism
MH  - Oxidation-Reduction
MH  - Oxidative Stress/*drug effects
MH  - Polychlorinated Biphenyls/*toxicity
MH  - Superoxides/metabolism
MH  - Swine
MH  - Time Factors
PMC - PMC3026064
MID - NIHMS262963
COIS- Conflict of Interest Statement The authors declare they have no actual or 
      potential competing financial interests.
EDAT- 2010/12/07 06:00
MHDA- 2011/02/25 06:00
PMCR- 2012/02/15
CRDT- 2010/12/07 06:00
PHST- 2010/07/01 00:00 [received]
PHST- 2010/11/22 00:00 [revised]
PHST- 2010/11/22 00:00 [accepted]
PHST- 2010/12/07 06:00 [entrez]
PHST- 2010/12/07 06:00 [pubmed]
PHST- 2011/02/25 06:00 [medline]
PHST- 2012/02/15 00:00 [pmc-release]
AID - S0041-008X(10)00445-X [pii]
AID - 10.1016/j.taap.2010.11.013 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2011 Feb 15;251(1):41-9. doi: 10.1016/j.taap.2010.11.013. 
      Epub 2010 Dec 1.