A combination of lactacystin and 12-O-tetradecanoylphorbol-13-acetate enhances the release of arachidonic acid from cells in cultures: release is reduced in confluent and serum deprived cells.
Lactacystin, a selective inhibitor of some proteasome activities, in the presence of 12-tetradecanoyl phorbol-13-acetate stimulates the release of arachidonic acid from the phospholipids of bovine pulmonary artery endothelial, bovine embryonic thoracic aorta smooth muscle, rat liver and rat glial cells. The enhanced release from rat liver cells is inhibited by dexamethasone, aspirin, Na salicylate and the immunosuppressive fungal metabolite, gliotoxin. The effects of aspirin plus dexamethasone are not additive, but those of gliotoxin plus dexamethasone are additive. The stimulated and unstimulated release from all four cells are decreased when these cells are grown to confluence or when they are growth arrested by serum deprivation. The unstimulated as well as the stimulated release is partially inhibited by the cytosolic phospholipase A2 inhibitor, methylarachidonyl fluorophosphonate. The enhanced release is reduced in the presence of the translation and transcription inhibitors, actinomycin and cycloheximide.
Levine
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Department of Biochemistry, Brandeis University, Waltham, Massachusetts 02254, USA. llevine@brandeis.edu
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000196:embryology; D016718:Arachidonic Acid / Q000378:metabolism*; D001095:Arachidonic Acids / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D003260:Contact Inhibition; D003470:Culture Media; D016895:Culture Media, Serum-Free; D003546:Cysteine Endopeptidases; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005912:Gliotoxin / Q000494:pharmacology; D054513:Group IV Phospholipases A2; D022781:Hepatocytes / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects; D063065:Organophosphonates; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D046988:Proteasome Endopeptidase Complex; D011651:Pulmonary Artery / Q000166:cytology; D051381:Rats; D012980:Sodium Salicylate / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D001095:Arachidonic Acids; D003470:Culture Media; D016895:Culture Media, Serum-Free; D015853:Cysteine Proteinase Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D009097:Multienzyme Complexes; D063065:Organophosphonates; C104810:methyl arachidonylfluorophosphonate; C067713:lactacystin; D016718:Arachidonic Acid; D005912:Gliotoxin; D003907:Dexamethasone; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex; D013755:Tetradecanoylphorbol Acetate; D001241:Aspirin; D012980:Sodium Salicylate; D000111:Acetylcysteine