Alterations of membrane integrity and cellular constituents by arachidonic acid in neuroblastoma and glioma cells.
Effects of arachidonic acid on cellular metabolism, cation content, lipid peroxidation, sodium pump activities and release of labeled arachidonic acid were studied in C-6 glioma cells and N18TG2 neuroblastoma cells. Arachidonic acid caused a significant increase in intracellular sodium levels concomitant with a decrease in intracellular potassium in both cell lines. Both (Na+ + K+)-ATPase and p-nitrophenyl phosphatase of glioma cells were inhibited by arachidonic acid whereas only the p-nitrophenyl phosphatase of neuroblastoma cell was inactivated. Low concentrations of arachidonic acid stimulated lactic acid release whereas high concentrations had an opposite effect. In addition, the lipid peroxide content of glioma cells was increased abruptly by 50 microM arachidonic acid whereas only a slight increase of malondialdehyde was observed in neuroblastoma cells. When the cultured cells of both cell lines were incubated with exogenous labeled arachidonic acid, 78-95% of the label was incorporated into membrane phospholipids. Only a very small fraction of prostaglandin E2 and prostaglandin F2 alpha was synthesized. Exogenous arachidonic acid and free radicals generated with xanthine-xanthine oxidase caused a significant release of endogenous labeled arachidonic acid from cellular membrane phospholipids. These data further support our hypothesis that the arachidonic acid and its oxygen radical metabolites induce pathological alterations in membrane permeability and cellular volume.
D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000378:metabolism*; D002460:Cell Line; D005609:Free Radicals; D005910:Glioma / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D013570:Synaptic Membranes / Q000187:drug effects*
D001095:Arachidonic Acids; D005609:Free Radicals; D007473:Ion Channels; D007773:Lactates; D008563:Membrane Lipids; D008315:Malondialdehyde; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium