Arachidonic acid oxidation by brain and placenta preparations from normal and placental insufficient fetal rabbit.
Cytosolic (100,000 g) fractions of fetal rabbit brain and placenta tissue convert [1-14C]arachidonic acid into several oxidation products identified with the lipoxygenase [12-hydroxyeicosatetraenoic acid (12-HETE) and 15-HETE] and cyclooxygenase [prostaglandin E2 (PGE2)] pathways. Formation of 12-HETE and 15-HETE by fetal brain is time-dependent, reaching a plateau after 40 min and is linear with protein concentration. An apparent affinity constant of 0.06 mM and a Vmax of 0.1 mumol/h/g wet weight are presumably responsible for the excessive accumulation of 12-HETE and 15-HETE in comparison to PGE2 (Km = 0.5 mM). The latter is synthesized by the placenta particulate fraction but almost exclusively by the brain cytosol. Compared to brain, the activity of the placenta tissue is exceedingly higher and in addition to 12-HETE and 15-HETE there is a substantial formation of 12-L-hydroxyheptadecatrienic acid. Formation of 12-HETE and 15-HETE at 21 days is as effective as at 31 days gestation and is strongly inhibited by nordihydroguaiaretic acid (93%), BW755c (99%), and AA861 (84%) but not by indomethacin. Placenta and brain tissues of intrauterine growth retarded fetuses after ligation of placental blood vessels fail to convert arachidonic acid into other eicosanoids. Loss of enzymatic activity also observed in normal tissue after prolonged storage cannot be restored by the addition of several SH agents, ascorbate, or ferric iron.
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001921:Brain / Q000196:embryology* / Q000378:metabolism; D015232:Dinoprostone; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D007700:Kinetics; D008084:Lipoxygenase / Q000378:metabolism; D010084:Oxidation-Reduction; D010920:Placenta / Q000378:metabolism*; D010922:Placenta Diseases / Q000378:metabolism*; D010927:Placental Insufficiency / Q000378:metabolism*; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011458:Prostaglandins E / Q000378:metabolism; D011817:Rabbits
D001095:Arachidonic Acids; D006893:Hydroxyeicosatetraenoic Acids; D011458:Prostaglandins E; D016718:Arachidonic Acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D008084:Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone