15S-HpETE

Folkerts, G. Nijkamp, F.J., and van Oosterhout, A.M.J. (1983). Induction in guinea-pigs of airway hyperreactitivity and decreased lung beta adrenoreceptor number by 15-HPETE. Br. J. Pharmacol. 80, 597-599. 

HODE Hydroxyoctadecanoic acid HO Hydroxyl radical H02 Perhydroxyl radical HPETE, 5-HPETE 15-HPETE... 

HPETE, 12(.S)-hydroperoxyeicosatetraenoic acid 15-HPETE, 15(S)-hydropcroxycicosatctracnoic acid 4-HPNE, 4-hydroperoxy-2-nonenal... 

FIGURE 26.4 Oxidation of 5-HPETE and 15-HPETE by LOX-15. (From DK MacMillan, E Hill, A Sala, E Sigal, T Shuman, PM Henson, RC Murphy. J Biol Chem 269 26663-26668, 1994. With permission.)... 

Glutathione peroxidase is a selenium-dependent enzyme, which rapidly detoxifies hydrogen peroxide and various hydroperoxides. Suttorp et al. [67] showed that the impairment of glutathione cycle resulted in an increase in the injury of pulmonary artery endothelial cells. Glutathione cycle protected against endothelial cell injury induced by 15-HPETE, an arachi-donate metabolite produced by 15-lipoxygenase-catalyzed oxidation [68]. 

HPCA ([4-(3-heptyl)pyridine-2-carboxylic add]), transihon metal peroxides, 1116 15-HPETE (155 -hydroperoxy-5,811z,... 

Next, 15-LOX oxidizes both 15-HPETE and 5-HPETE to LTA4 (Figure 26.4). Rat peritoneal monocytes and human leukocytes are also able to oxidize AA into the dihydroxy derivative, 5(S), 15(,V)-dihydroxy-6,l 3-/ran.v-8,11 -c/.v-cicosatctracnoic acid (5,15-DiHETE). It has been shown [18] that 5,15-DiHETE was formed by a double oxidation of AA catalyzed by both 5-LOX and 15-LOX lipoxygenases (Figure 26.5). It is interesting that the... 

Enzyme Assays. Cytochrome P-450 peroxidase activity was determined by the method of O Brien and Rahimthula (27) as modified by Reddy, et al, with cumene hydroperoxide (CHP), linoleic acid hydroperoxide (LHP) and 15-HPETE as substrates and tetramethyl-P-phenylene diamine (TMPD) as electron donor. Prostaglandin H synthase activity was measured as previously described (19). 

Values with H202 were subtracted from those of CHP to obtain Non-Se-GSH-Px activities as previously described (1 8). However, from our previous experience, the estimation of non-Se-GSH-Px activity with fatty acid hydroperoxides could not be done in a similar way. Because, catalytic rates of purified Se-GSH-Px toward LHP and 15-HPETE are not identical with those for H202 whereas CHP and H202 exhibit identical rates (13 32). This is further complicated by the presence of different Non-Se-GSH-Px isozymes exhibiting different catalytic rates toward fatty acid hydroperoxides (33). Therefore, the values for LHP and 15-HPETE are presented as total GSH-Px activity rather than individually. 

Table VI summarizes total GSH-Px activity toward LHP and 15-HPETE in tissues from rats fed on vitamin E and/or Se deficient diets. GSH-Px activity toward fatty acid hydroperoxides was reduced markedly in liver and lung under Se-deficient states whereas kidney enzyme levels were only marginally affected. It should be noted that these total enzyme activities were contributed by both Se-GSH-Px and non-Se GSH-Px in crude cytosols of Se supplemented animals. However, in Se-deficient...

Lipoxygenase pathway Alternatively, several lipoxygenases can act on arachidonic acid to form 5-HPETE, 12-HPETE and 15-HPETE, which are unstable peroxidated derivatives that are converted to the corresponding hydroxylated derivatives (the HETES), or to leukotrienes or lipoxins, depending on the tissue (Figure 39.3).2... 

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