Emerging mechanisms for growth and protection of the vasculature by cytochrome P450-derived products of arachidonic acid and other eicosanoids

Expression of CYP4A1 in U251 Human Glioma Cell Induces Hyperproliferative Phenotype in Vitro and Rapidly Growing Tumors in Vivo

“…Previous studies have indicated that 20-HETE is produced by vascular and brain tissue (Roman, 2002;Metea and Newman, 2006;Gordon et al, 2007;Medhora et al, 2007b). We have shown that the addition of a single dose of a 20-HETE analog to the cell media transiently stimulates the proliferation of U251 human glioma cells in vitro (Guo et al, 2005a,b).…”

Multiple antiapoptotic targets of the PI3K/Akt survival pathway are activated by epoxyeicosatrienoic acids to protect cardiomyocytes from hypoxia/anoxia

“…A recent finding in a renal proximal tubular epithelial cell line demonstrated that EETs inhibit apoptosis induced by serum withdrawal and etoposide (6,41). We have reported that EETs inhibit apoptosis induced by the engagement of the death receptor Fas or by serum withdrawal in human vascular endothelial cells cultured from the heart or lung (17,36). Hence, we were interested to see whether EETs have the same antiapoptotic effect in cardiomyocytes after I/R since myocardial cell death caused by apoptosis is a main feature of this condition.…”

“…The lysates were used to estimate protein content with the Bio-Rad DC Protein Assay reagent (Bio-Rad, Hercules, CA). Equal amounts of protein (10 -60 g) from each sample were electrophoresed on a 10% SDS-PAGE with running buffer and transferred to nitrocellulose as described (17,36). The membranes were treated with primary antibody for XIAP, pBAD, BAD, or pAkt (1:1,000 dilution; Cell Signaling) for 18 h. They were again washed three times before incubating with matched secondary antibody (1: 5,000) for 45 min.…”

CYP4F3B is induced by PGA1 in human liver cells: a regulation of the 20-HETE synthesis

“…Furthermore, in several pathological conditions, including hyperthermia, infection, or inflammation, local prostaglandin concentrations in the micromolar range can be detected (36). Indeed, while other eicosanoids, such as leukotrienes and lipoxins, usually evoke bioactions in the nanomolar or subnanomolar range in vivo, PGs mostly require micromolar concentrations to elicit biological effects (29,(38)(39)(40)(41). It remains to be determined if the level of PGA 1 required to achieve a sufficiently high local concentration in vivo to induce 20-HETE production in target cells or tissues can indeed be reached.…”

“…20-HETE could participate in the modulation of liver diseases and in the renal functional disturbances in patients with hepatic cirrhosis (40). 20-HETE has also been shown to promote cell growth and angiogenesis (41). As prostaglandin and leukotriene hydroxylases, CYP4F enzymes can modulate the levels of eicosanoids during inflammation (1).…”