Oxidant stress inhibits the endogenous production of lipoxygenase metabolites in rat lungs and fish gills.
Hydroperoxides are potent initiators of lipid peroxidation in vivo. Acyl hydroperoxides may also regulate various aspects of lipid metabolism. In this study we investigated the regulation of the endogenous 12 lipoxygenase in trout gill and rat lung, a prominent acyl hydroperoxide catalyst in these tissues. Initial experiments revealed that the enzyme from trout gill was activated by hydroperoxides at low levels and inactivated by the same hydroperoxides at high levels. Homogenization of these tissues resulted in the production of a predominant metabolite class from released endogenous polyunsaturated fatty acids, the 12 lipoxygenase products. In rat lung, arachidonic acid was the major polyunsaturated fatty acid released and 12 (S) HETE was the major metabolite. In trout gill 20:4, 20:5 n3, and 22:6 n3 were released and the 12(S), 12, and 14 hydroxy derivatives the corresponding metabolites. Computer simulations of the sensitivity of these enzymes to hydroperoxides predicted that exogenous oxidant stress would reduce significantly the production of HETEs. Tertiary butyl hydroperoxide was added to tissue homogenates and resulted in elimination of greater than 95% of the lipoxygenase activity. These results suggest that the lipoxygenase enzyme in lung and gill tissue is a major potential source for acyl hydroperoxides in vivo, but is also very sensitive to oxidant stresses including the acyl hydroperoxides themselves. This enzyme could thus be an important focus for oxidant injury in lungs.
German
J B
JB
Department of Food Science and Technology, University of California-Davis 95616.
Hu
M L
ML
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D006051:Aurothioglucose / Q000494:pharmacology; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D008401:Gas Chromatography-Mass Spectrometry; D005880:Gills / Q000187:drug effects / Q000201:enzymology*; D005979:Glutathione Peroxidase / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D012643:Selenium / Q000494:pharmacology; D014337:Trout
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D006051:Aurothioglucose; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D001092:Arachidonate 12-Lipoxygenase; D012643:Selenium