Article
Cytochrome P450 epoxygenases, soluble epoxide hydrolase, and the regulation of cardiovascular inflammation.
Division of Pharmacotherapy and Experimental Therapeutics, UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, NC 27599-7569, USA.
Journal of Molecular and Cellular Cardiology (impact factor:
5.17).
11/2009;
48(2):331-41.
DOI:10.1016/j.yjmcc.2009.10.022
pp.331-41
Source: PubMed
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ABSTRACT: The c-Myc protein is a member of the basic region/helix-loop-helix/leucine zipper (bHLHZip) transcription factor family, which is implicated in regulation of proliferation, differentiation, and apoptosis in multiple cell types. The aim of this study was to characterize the role of the proto-oncogene c-myc in hematopoietic stem cells (HSC) during postnatal development. We have generated a conditional mouse model that allows us to inactivate c-myc in bone marrow (BM) in an inducible fashion. We show that conditional inactivation of c-Myc in BM severely impairs HSC differentiation, leading to a striking decrease in the number of lymphoid and myeloid cells. c-Myc deletion in BM causes substantial accumulation of a Lin(-)Sca-1(+)c-Kit(-) cell population expressing high levels of the cell-cycle inhibitor p21, whose origin and function are otherwise poorly characterized. In vivo inactivation of p21 and c-Myc normalizes Lin(-)Sca-1(+)c-Kit(-) cell numbers and restores normal proliferation. The potential origin and function of these cells are discussed. c-Myc plays a role in HSC maintenance and differentiation and might be regulating generation of Lin(-)Sca-1(+)c-Kit(-) through the cell-cycle regulator p21.Experimental Hematology 10/2007; 35(9):1333-43. · 2.90 Impact Factor -
Article: Cytochrome P450 2C is an EDHF synthase in coronary arteries.
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ABSTRACT: In most arterial beds a significant endothelium-dependent dilation to various stimuli persists even after inhibition of nitric oxide synthase and cyclo-oxygenase. This dilator response is preceded by an endothelium-dependent hyperpolarization of vascular smooth muscle cells, which is sensitive to a combination of the calcium-dependent potassium-channel inhibitors charybdotoxin and apamin, and is assumed to be mediated by an unidentified endothelium-derived hyperpolarizing factor (EDHF). Here we show that the induction of cytochrome P450 (CYP) 2C8/34 in native porcine coronary artery endothelial cells by beta-naphthoflavone enhances the formation of 11,12-epoxyeicosatrienoic acid, as well as EDHF-mediated hyperpolarization and relaxation. Transfection of coronary arteries with CYP 2C8/34 antisense oligonucleotides results in decreased levels of CYP 2C and attenuates EDHF-mediated vascular responses. Thus, a CYP-epoxygenase product is an essential component of EDHF-mediated relaxation in the porcine coronary artery, and CYP 2C8/34 fulfils the criteria for the coronary EDHF synthase.Nature 10/1999; 401(6752):493-7. · 36.28 Impact Factor
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Keywords
arachidonic acid
cardiovascular protective effects
CYP epoxygenase-derived EET biosynthesis
CYP2C catalyze
dihydroxyeicosatrienoic acids
emerging target
endothelial activation
endothelial cell survival
epoxyeicosatrienoic acids
future research
key inflammatory process
leukocyte adhesion
multiple cell signaling pathways
myocardial ischemia-reperfusion injury
nuclear factor-kappaB activation
potent vasodilatory effects
recent years
sEH-mediated EET hydrolysis
soluble epoxide hydrolase
various inflammatory processes