Aplysia californica contains a novel 12-lipoxygenase which generates biologically active products from arachidonic acid.

Abstract

Physiologic stimulation of identified neurons in ganglia of the marine mollusk, Aplysia californica, leads to the generation of arachidonic acid metabolites. Using various preparations of Aplysia nervous tissue, we have identified 12-lipoxygenase products including the inactive 12-hydroxyeicosatetraenoic acid (12-HETE) and the biologically active 12-ketoeicosatetraenoic acid (12-KETE) and 8-hydroxy-11(12)-epoxyeicosatrienoic acid (8-HEpETE). Each of these metabolites can be derived from the intermediate 12-hydroperoxyeicosatetraenoic acid (12-HPETE), which can itself activate several identified neurons in Aplysia. In spite of conflicting results in studies of mammalian brain 12-lipoxygenase, Aplysia nervous tissue clearly contains an enzymatic activity which generates stereochemically pure 12(S)-HETE. This activity is destroyed by boiling and is sensitive to nonspecific lipoxygenase inhibitors but not to agents specific for other lipoxygenases or the cyclooxygenase enzyme. The Aplysia 12-lipoxygenase is highly enriched in neural tissue and is almost completely absent in the neural sheath, which is composed primarily of connective tissue and muscle. Preliminary purification has shown that, in contrast to the previously characterized 12-lipoxygenases, the Aplysia enzyme is associated with membrane fractions and is not found in the cytosol. Further studies are in progress to determine the kinetic properties and to define the cellular and subcellular distribution of this novel lipoxygenase.