HETE signaling

One possible integrator of these 12(S)-HETE signaling mechanisms in tumor cells is the pleiotropic transcription factor NE-kB, which plays an important role in the control of cell proliferation and apoptosis. Using PC-3 prostate cancer cells, we have shown that either overexpression of the platelet-type 12-LOX or exogenously added 12(S)-HETE activates NF-kB (Kandouz et al.,... 

Disturbances in lipid metabolism occur in the skin in psoriasis. Increased phospholipase A2 activity is seen in lesional and nonlesional skin, while phospholipase C activity is elevated in lesional skin.183-184 Increased elongase activity is also observed in psoriatic epidermis. A local increase in AA occurs, and this appears to be preferentially metabolized by the lipoxygenases, resulting in a marked increase in 12-HETE and LTB4, while there appears to be a relative or absolute reduction in metabolism by the COX pathway.185 Leukotriene B4 is a very potent chemoattractant, and topical application causes epidermal hyperproliferation in addition to neutrophil microabscesses.186 A defective transmembranous cell-signaling system is also suggested by elevation of both IP3 and DAG in the psoriatic plaque.187... 

The accurate measurement of the concentration of DNA appeared to be essential because of the strong dependence of the chemiluminescence signal upon the amount of DNA blotted on the filter. Approximately, a 2-fold increase in the amount of DNA resulted in a 4-fold increase of the chemiluminescence signal. For that reason we decided to blot, as a standard procedure, 1 pg DNA/blot instead of various amounts of DNA and to reserve 10 positions on the 96-blots filter for calibration samples of DNA with adduct levels in the range of 0-10 N7-HETE-dG/107 nucleotides. 

Alexanian, A., V. A. Rufanova et al. 2009. Down-regulation of 20-HETE synthesis and signaling inhibits renal adenocarcinoma cell proliferation and tumor growth. Anticancer Res 29(10) 3819-3824. 

The metabolism of 12(S)-HPETE, illustrated in Figure 4.21, yields two main classes of compounds. The enzymatic reduction of 12(S)-HPETE by glutathione peroxidases gives rise to 12(S)-HETE, a signaling molecule involved in cell proliferation and adhesion. Alternatively, structural rearrangements of the hydroperoxy moiety of 12(S)-HPETE produce two distinct hydroxy-epoxides, hepoxilin A3... 

---