PMID- 19540314
OWN - NLM
STAT- MEDLINE
DCOM- 20091214
LR  - 20220310
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Linking)
VI  - 163
IP  - 2
DP  - 2009 Oct 6
TI  - Distribution of soluble and microsomal epoxide hydrolase in the mouse brain and 
      its contribution to cerebral epoxyeicosatrienoic acid metabolism.
PG  - 646-61
LID - 10.1016/j.neuroscience.2009.06.033 [doi]
AB  - Epoxide hydrolases comprise a family of enzymes important in detoxification and 
      conversion of lipid signaling molecules, namely epoxyeicosatrienoic acids (EETs), 
      to their supposedly less active form, dihydroxyeicosatrienoic acids (DHETs). EETs 
      control cerebral blood flow, exert analgesic, anti-inflammatory and angiogenic 
      effects and protect against ischemia. Although the role of soluble epoxide 
      hydrolase (sEH) in EET metabolism is well established, knowledge on its detailed 
      distribution in rodent brain is rather limited. Here, we analyzed the expression 
      pattern of sEH and of another important member of the EH family, microsomal 
      epoxide hydrolase (mEH), in mouse brain by immunohistochemistry. To investigate 
      the functional relevance of these enzymes in brain, we explored their individual 
      contribution to EET metabolism in acutely isolated brain cells from respective EH 
      -/- mice and wild type littermates by mass spectrometry. We find sEH 
      immunoreactivity almost exclusively in astrocytes throughout the brain, except in 
      the central amygdala, where neurons are also positive for sEH. mEH 
      immunoreactivity is abundant in brain vascular cells (endothelial and smooth 
      muscle cells) and in choroid plexus epithelial cells. In addition, mEH 
      immunoreactivity is present in specific neuronal populations of the hippocampus, 
      striatum, amygdala, and cerebellum, as well as in a fraction of astrocytes. In 
      freshly isolated cells from hippocampus, where both enzymes are expressed, sEH 
      mediates the bulk of EET metabolism. Yet we observe a significant contribution of 
      mEH, pointing to a novel role of this enzyme in the regulation of physiological 
      processes. Furthermore, our findings indicate the presence of additional, 
      hitherto unknown cerebral epoxide hydrolases. Taken together, cerebral EET 
      metabolism is driven by several epoxide hydrolases, a fact important in view of 
      the present targeting of sEH as a potential therapeutic target. Our findings 
      suggest that these different enzymes have individual, possibly quite distinct 
      roles in brain function and cerebral EET metabolism.
FAU - Marowsky, A
AU  - Marowsky A
AD  - Institute of Pharmacology and Toxicology, University of Zurich, Winterthurerstr. 
      190, CH-8057 Zurich, Switzerland. marowsky@pharma.uzh.ch
FAU - Burgener, J
AU  - Burgener J
FAU - Falck, J R
AU  - Falck JR
FAU - Fritschy, J-M
AU  - Fritschy JM
FAU - Arand, M
AU  - Arand M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090618
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Eicosanoids)
RN  - 0 (Epoxy Compounds)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
SB  - IM
MH  - Animals
MH  - Astrocytes/enzymology/metabolism
MH  - Blood Vessels/enzymology/metabolism
MH  - Brain/blood supply/enzymology/*metabolism
MH  - Cells, Cultured
MH  - Choroid Plexus/enzymology/metabolism
MH  - Eicosanoids/*metabolism
MH  - Epithelial Cells/enzymology/metabolism
MH  - Epoxide Hydrolases/genetics/*metabolism
MH  - Epoxy Compounds/*metabolism
MH  - Female
MH  - Immunohistochemistry
MH  - Male
MH  - Mass Spectrometry
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocytes, Smooth Muscle/enzymology/metabolism
MH  - Neurons/enzymology/metabolism
MH  - Sex Characteristics
EDAT- 2009/06/23 09:00
MHDA- 2009/12/16 06:00
CRDT- 2009/06/23 09:00
PHST- 2008/12/23 00:00 [received]
PHST- 2009/06/05 00:00 [revised]
PHST- 2009/06/07 00:00 [accepted]
PHST- 2009/06/23 09:00 [entrez]
PHST- 2009/06/23 09:00 [pubmed]
PHST- 2009/12/16 06:00 [medline]
AID - S0306-4522(09)01058-6 [pii]
AID - 10.1016/j.neuroscience.2009.06.033 [doi]
PST - ppublish
SO  - Neuroscience. 2009 Oct 6;163(2):646-61. doi: 10.1016/j.neuroscience.2009.06.033. 
      Epub 2009 Jun 18.