Ca2+-independent phospholipases A2 and production of arachidonic acid in nuclei of LA-N-1 cell cultures:: a specific receptor activation mediated with retinoic acid

The LA-N-1 cell nucleus contains Ca2+-independent phospholipase A(2) (PLA(2)) activity hydrolyzing plasmenylethanolamine (PlsEtn) and 1,2-diacyl-sn-glycero-3-phosphoethanolamine (PtdEtn). These enzymes hydrolyze glycerophospholipids to produce arachidonic acid and lysoglycerophospholipids. The treatment of LA-N-1 cell cultures with all-trans retinoic acid (atRA) results in time- and dose-dependent stimulation of PlsEtn-PLA(2) and PtdEtn-PLA(2) activities in the nuclear fraction. PLA(2) activities in the non-nuclear fraction (microsomes) are not affected by atRA, whilst the pan retinoic acid receptor (RAR) antagonist, BMS493, blocks the PLA(2) activities in the nuclear fraction. This indicates that the stimulation of PLA(2) activities is a receptor-mediated process. Treatment of LA-N-1 cell cultures with cycloheximide has no effect on basal PLA(2) activities. However, atRA-mediated stimulation of PLA(2) activities in LA-N-1 cell nuclei is partially inhibited by cycloheximide indicating that this decrease in PLA(2) activity is due to a general decreased protein synthesis. Our results also support earlier studies in which atRA induces morphologic differentiation through the stimulation of PLA(2)-generated second messengers such as arachidonic acid and eicosanoids. (C) 2003 Elsevier B.V. All rights reserved.