PMID- 28292183
OWN - NLM
STAT- MEDLINE
DCOM- 20171025
LR  - 20180223
IS  - 1948-7193 (Electronic)
IS  - 1948-7193 (Linking)
VI  - 8
IP  - 3
DP  - 2017 Mar 15
TI  - N-Docosahexaenoyl Dopamine, an Endocannabinoid-like Conjugate of Dopamine and the 
      n-3 Fatty Acid Docosahexaenoic Acid, Attenuates Lipopolysaccharide-Induced 
      Activation of Microglia and Macrophages via COX-2.
PG  - 548-557
LID - 10.1021/acschemneuro.6b00298 [doi]
AB  - Several studies indicate that the n-3 long-chain polyunsaturated fatty acid 
      docosahexaenoic acid (DHA) contributes to an attenuated inflammatory status in 
      the development of neurodegenerative disorders, such as Alzheimer's and 
      Parkinson's disease. To explain these effects, different mechanisms are being 
      proposed, including those involving endocannabinoids and related signaling 
      molecules. Many of these compounds belong to the fatty acid amides, conjugates of 
      fatty acids with biogenic amines. Conjugates of DHA with ethanolamine or 
      serotonin have previously been shown to possess anti-inflammatory and potentially 
      neuroprotective properties. Here, we synthesized another amine conjugate of DHA, 
      N-docosahexaenoyl dopamine (DHDA), and tested its immune-modulatory properties in 
      both RAW 264.7 macrophages and BV-2 microglial cells. N-Docosahexaenoyl dopamine 
      significantly suppressed the production of nitric oxide (NO), the cytokine 
      interleukin-6 (IL-6), and the chemokines macrophage-inflammatory protein-3alpha 
      (CCL20) and monocyte chemoattractant protein-1 (MCP-1), whereas its parent 
      compounds, dopamine and DHA, were ineffective. Further exploration of potential 
      effects of DHDA on key inflammatory mediators revealed that cyclooxygenase-2 
      (COX-2) mRNA level and production of prostaglandin E(2) (PGE(2)) were 
      concentration-dependently inhibited in macrophages. In activated BV-2 cells, 
      PGE(2) production was also reduced, without changes in COX-2 mRNA levels. In 
      addition, DHDA did not affect NF-kB activity in a reporter cell line. Finally, 
      the immune-modulatory activities of DHDA were compared with those of 
      N-arachidonoyl dopamine (NADA) and similar potencies were found in both cell 
      types. Taken together, our data suggest that DHDA, a potentially endogenous 
      endocannabinoid, may be an additional member of the group of immune-modulating 
      n-3 fatty acid-derived lipid mediators.
FAU - Wang, Ya
AU  - Wang Y
AUID- ORCID: 0000-0002-8886-9936
FAU - Plastina, Pierluigi
AU  - Plastina P
AD  - Department of Chemistry and Chemical Technologies, University of Calabria , 87036 
      Cosenza, Italy.
FAU - Vincken, Jean-Paul
AU  - Vincken JP
FAU - Jansen, Renate
AU  - Jansen R
FAU - Balvers, Michiel
AU  - Balvers M
FAU - Ten Klooster, Jean Paul
AU  - Ten Klooster JP
AD  - Research Centre Technology & Innovation, Innovative Testing in Life Sciences and 
      Chemistry, University of Applied Sciences , 3584 CH Utrecht, The Netherlands.
FAU - Gruppen, Harry
AU  - Gruppen H
FAU - Witkamp, Renger
AU  - Witkamp R
FAU - Meijerink, Jocelijn
AU  - Meijerink J
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161206
PL  - United States
TA  - ACS Chem Neurosci
JT  - ACS chemical neuroscience
JID - 101525337
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (N-docosahexaenoyl dopamine)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 25167-62-8 (Docosahexaenoic Acids)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Cell Line, Transformed
MH  - Cyclooxygenase 2/genetics/*metabolism
MH  - Cytokines/metabolism
MH  - Dinoprostone/metabolism
MH  - Docosahexaenoic Acids/*pharmacology
MH  - Dopamine/*analogs & derivatives/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Macrophages/*drug effects/metabolism
MH  - Mice
MH  - Microglia/*drug effects/metabolism
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/metabolism
MH  - RNA, Messenger/metabolism
MH  - Statistics, Nonparametric
OTO - NOTNLM
OT  - Endocannabinoids
OT  - N-arachidonoyl dopamine
OT  - N-docosahexaenoyl dopamine
OT  - cyclooxygenase-2
OT  - interleukin-6
OT  - prostaglandin E2
EDAT- 2017/03/16 06:00
MHDA- 2017/10/27 06:00
CRDT- 2017/03/16 06:00
PHST- 2017/03/16 06:00 [entrez]
PHST- 2017/03/16 06:00 [pubmed]
PHST- 2017/10/27 06:00 [medline]
AID - 10.1021/acschemneuro.6b00298 [doi]
PST - ppublish
SO  - ACS Chem Neurosci. 2017 Mar 15;8(3):548-557. doi: 10.1021/acschemneuro.6b00298. 
      Epub 2016 Dec 6.