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 A2 (PLA2) 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-PLA2 and PtdEtn-PLA2 activities in the nuclear fraction. PLA2 activities in the non-nuclear fraction (microsomes) are not affected by atRA, whilst the pan retinoic acid receptor (RAR) antagonist, BMS493, blocks the PLA2 activities in the nuclear fraction. This indicates that the stimulation of PLA2 activities is a receptor-mediated process. Treatment of LA-N-1 cell cultures with cycloheximide has no effect on basal PLA2 activities. However, atRA-mediated stimulation of PLA2 activities in LA-N-1 cell nuclei is partially inhibited by cycloheximide indicating that this decrease in PLA2 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 PLA2-generated second messengers such as arachidonic acid and eicosanoids.
Antony
Pierre
P
Laboratoire de Neurobiologie Moléculaire des Interactions Cellulaires, Institut de Chimie Biologique, Faculté de Médecine, 11 rue Humann, Strasbourg, France.
Freysz
Louis
L
Horrocks
Lloyd A
LA
Farooqui
Akhlaq A
AA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D009447:Neuroblastoma; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011500:Protein Synthesis Inhibitors; D018168:Receptors, Retinoic Acid; D016718:Arachidonic Acid; D014212:Tretinoin; D003513:Cycloheximide; D010741:Phospholipases A; D054467:Phospholipases A2