PMID- 21164107
OWN - NLM
STAT- MEDLINE
DCOM- 20110414
LR  - 20211020
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 108
IP  - 3
DP  - 2011 Feb 4
TI  - Redox regulation of soluble epoxide hydrolase by 15-deoxy-delta-prostaglandin J2 
      controls coronary hypoxic vasodilation.
PG  - 324-34
LID - 10.1161/CIRCRESAHA.110.235879 [doi]
AB  - RATIONALE: 15-Deoxy-Delta-prostaglandin (15d-PG)J(2) is an electrophilic oxidant that 
      dilates the coronary vasculature. This lipid can adduct to redox active protein 
      thiols to induce oxidative posttranslational modifications that modulate protein 
      and tissue function. OBJECTIVE: To investigate the role of oxidative protein 
      modifications in 15d-PGJ(2)-mediated coronary vasodilation and define the distal 
      signaling pathways leading to enhanced perfusion. METHODS AND RESULTS: Proteomic 
      screening with biotinylated 15d-PGJ(2) identified novel vascular targets to which 
      it adducts, most notably soluble epoxide hydrolase (sEH). 15d-PGJ(2) inhibited 
      sEH by specifically adducting to a highly conserved thiol (Cys521) adjacent to 
      the catalytic center of the hydrolase. Indeed a Cys521Ser sEH "redox-dead" mutant 
      was resistant to 15d-PGJ(2)-induced hydrolase inhibition. 15d-PGJ(2) dilated 
      coronary vessels and a role for hydrolase inhibition was supported by 2 
      structurally different sEH antagonists each independently inducing 
      vasorelaxation. Furthermore, 15d-PGJ(2) and sEH antagonists also increased 
      coronary effluent epoxyeicosatrienoic acids consistent with their vasodilatory 
      actions. Indeed 14,15-EET alone induced relaxation and 15d-PGJ(2)-mediated 
      vasodilation was blocked by the EET receptor antagonist 
      14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE). Additionally, the coronary 
      vasculature of sEH-null mice was basally dilated compared to wild-type controls 
      and failed to vasodilate in response to 15d-PGJ(2). Coronary vasodilation to 
      hypoxia in wild-types was accompanied by 15d-PGJ(2) adduction to and inhibition 
      of sEH. Consistent with the importance of hydrolase inhibition, sEH-null mice 
      failed to vasodilate during hypoxia. CONCLUSION: This represents a new paradigm 
      for the regulation of sEH by an endogenous lipid, which is integral to the 
      fundamental physiological response of coronary hypoxic vasodilation.
FAU - Charles, Rebecca L
AU  - Charles RL
AD  - King's College London, Cardiovascular Division, The Rayne Institute, St Thomas 
      Hospital, London, SE1 7EH, United Kingdom.
FAU - Burgoyne, Joseph R
AU  - Burgoyne JR
FAU - Mayr, Manuel
AU  - Mayr M
FAU - Weldon, Steven M
AU  - Weldon SM
FAU - Hubner, Norbert
AU  - Hubner N
FAU - Dong, Hua
AU  - Dong H
FAU - Morisseau, Christophe
AU  - Morisseau C
FAU - Hammock, Bruce D
AU  - Hammock BD
FAU - Landar, Aimee
AU  - Landar A
FAU - Eaton, Philip
AU  - Eaton P
LA  - eng
GR  - G0700320/MRC_/Medical Research Council/United Kingdom
GR  - PG/10/98/28655/BHF_/British Heart Foundation/United Kingdom
GR  - R01 ES002710-32/ES/NIEHS NIH HHS/United States
GR  - R01 ES002710/ES/NIEHS NIH HHS/United States
GR  - G0600785/MRC_/Medical Research Council/United Kingdom
GR  - P42 ES004699/ES/NIEHS NIH HHS/United States
GR  - FS/08/002/24537/BHF_/British Heart Foundation/United Kingdom
GR  - R37 ES002710/ES/NIEHS NIH HHS/United States
GR  - P42 ES004699-25/ES/NIEHS NIH HHS/United States
GR  - R01 ES002710-31/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101216
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (15-deoxyprostaglandin J2)
RN  - EC 3.3.2.- (Epoxide Hydrolases)
RN  - RXY07S6CZ2 (Prostaglandin D2)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Epoxide Hydrolases/analysis/genetics/*metabolism
MH  - Hypoxia/*metabolism/physiopathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Molecular Sequence Data
MH  - Myocardium/*metabolism
MH  - Oxidation-Reduction
MH  - Prostaglandin D2/*analogs & derivatives/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Signal Transduction
MH  - Vasodilation/*physiology
PMC - PMC3259859
MID - NIHMS348906
EDAT- 2010/12/18 06:00
MHDA- 2011/04/16 06:00
PMCR- 2012/01/17
CRDT- 2010/12/18 06:00
PHST- 2010/12/18 06:00 [entrez]
PHST- 2010/12/18 06:00 [pubmed]
PHST- 2011/04/16 06:00 [medline]
PHST- 2012/01/17 00:00 [pmc-release]
AID - CIRCRESAHA.110.235879 [pii]
AID - 10.1161/CIRCRESAHA.110.235879 [doi]
PST - ppublish
SO  - Circ Res. 2011 Feb 4;108(3):324-34. doi: 10.1161/CIRCRESAHA.110.235879. Epub 2010 
      Dec 16.