PMID- 20130225
OWN - NLM
STAT- MEDLINE
DCOM- 20100415
LR  - 20211020
IS  - 1522-1490 (Electronic)
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 298
IP  - 4
DP  - 2010 Apr
TI  - Roles of CYP2C29 and RXR gamma in vascular EET synthesis of female mice.
PG  - R862-9
LID - 10.1152/ajpregu.00575.2009 [doi]
AB  - We aimed to identify which cytochrome P-450 (CYP) family/subfamily, as well as 
      related transcription factor(s), is responsible for the estrogen-dependent 
      synthesis of epoxyeicosatrienoic acids (EETs) to initiate shear stress-induced 
      vasodilation. Microarray analysis indicated a significant upregulation of CYP2C29 
      and retinoid X receptor gamma (RXRgamma) in isolated mesenteric 
      arteries/arterioles of female endothelial nitric oxide synthase-knockout mice, a 
      result that was validated by real-time RT-PCR. The cannulated vessels were then 
      perfused with 2 and 10 dyn/cm(2) shear stress, followed by collection of the 
      perfusate to determine EET concentrations and isoforms. Shear stress 
      dose-dependently stimulated the release of EETs into the perfusate, associated 
      with an EET-mediated vasodilation, in which predominantly 14,15-EET and 11,12-EET 
      contributed to the responses ( approximately 87.4% of total EETs). Transfection 
      of vessels with CYP2C29 siRNA eliminated the release of EETs into the perfusate, 
      which was evidenced by an abolished vasodilation, and confirmed by RT-PCR and 
      Western blot analyses. Knockdown of RXRgamma in these vessels significantly 
      inhibited the production of EETs, parallel to a reduced vasodilation. RXRgamma 
      siRNA not only silenced the vascular RXRgamma expression, but synchronously 
      downregulated CYP2C29 expression, leading to a reduced EET synthesis. In 
      conclusion, our data provide the first evidence for a specific signaling cascade, 
      by which estrogen potentially activates the CYP2C29 gene in the absence of nitric 
      oxide, to synthesize EETs in response to shear stress, via an RXRgamma-related 
      regulatory mechanism.
FAU - Sun, Dong
AU  - Sun D
AD  - Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
FAU - Yang, Yang-Ming
AU  - Yang YM
FAU - Jiang, Houli
AU  - Jiang H
FAU - Wu, Hongyan
AU  - Wu H
FAU - Ojaimi, Caroline
AU  - Ojaimi C
FAU - Kaley, Gabor
AU  - Kaley G
FAU - Huang, An
AU  - Huang A
LA  - eng
GR  - R01 HL070653-06/HL/NHLBI NIH HHS/United States
GR  - P01 HL034300/HL/NHLBI NIH HHS/United States
GR  - HL070653/HL/NHLBI NIH HHS/United States
GR  - ImNIH/Intramural NIH HHS/United States
GR  - R01 HL070653/HL/NHLBI NIH HHS/United States
GR  - HL43023/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
DEP - 20100203
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Hydroxyeicosatetraenoic Acids)
RN  - 0 (Retinoid X Receptor gamma)
RN  - 63231-63-0 (RNA)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.14.1 (Cyp2c29 protein, mouse)
RN  - EC 1.14.14.1 (Cytochrome P450 Family 2)
SB  - IM
MH  - Animals
MH  - Arterioles/physiology
MH  - Cytochrome P-450 Enzyme System/*genetics
MH  - Cytochrome P450 Family 2
MH  - Fatty Acids, Unsaturated/biosynthesis
MH  - Female
MH  - Hydroxyeicosatetraenoic Acids/biosynthesis/*physiology
MH  - Male
MH  - Mesenteric Arteries/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Nitric Oxide Synthase/deficiency
MH  - Nucleic Acid Hybridization
MH  - Oligonucleotide Array Sequence Analysis
MH  - RNA/genetics/isolation & purification
MH  - RNA Interference
MH  - Retinoid X Receptor gamma/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sex Characteristics
MH  - Vasodilation
PMC - PMC2853397
EDAT- 2010/02/05 06:00
MHDA- 2010/04/16 06:00
PMCR- 2011/04/01
CRDT- 2010/02/05 06:00
PHST- 2010/02/05 06:00 [entrez]
PHST- 2010/02/05 06:00 [pubmed]
PHST- 2010/04/16 06:00 [medline]
PHST- 2011/04/01 00:00 [pmc-release]
AID - 00575.2009 [pii]
AID - R-00575-2009 [pii]
AID - 10.1152/ajpregu.00575.2009 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2010 Apr;298(4):R862-9. doi: 
      10.1152/ajpregu.00575.2009. Epub 2010 Feb 3.