arachidonyltrifluoromethane and fluorexon

Nontoxic concentrations of peroxynitrite (ONOO(-)) nevertheless commit rat astrocytes to mitochondrial permeability transition-dependent toxicity, however prevented by a signaling response driven by arachidonic acid (ARA). The lipid messenger was released upon ONOO(-)-dependent activation of cytosolic phospholipase A(2) and its pharmacological inhibition, or knock-down, was invariably associated with a prompt apoptotic response sensitive to exogenous ARA, but insensitive to other polyunsaturated fatty acids, as eicosapentaenoic or linoleic acid. Interestingly, while microglia also used ARA to cope with ONOO(-), cerebellar granule cells were killed by the same concentrations of ONOO(-) employed in astrocyte/microglia experiments via a mechanism sensitive to inhibition of ARA release. These results collectively support the notion that resistance of glial cells to ONOO(-), a species extensively produced under neuroinflammatory conditions, is largely based on a critical survival signaling triggered by the inflammatory product ARA. In remarkable contrast with these results, the lipid messenger appears to mediate toxicity in neuronal cells.

Topics: Adenosine Triphosphate; Analysis of Variance; Animals; Animals, Newborn; Arachidonic Acid; Arachidonic Acids; Astrocytes; Caspase 3; Cell Survival; Cells, Cultured; Cerebellum; Cerebral Cortex; Cytochromes c; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fluoresceins; Membrane Potential, Mitochondrial; Neurons; Oligodeoxyribonucleotides, Antisense; Peroxynitrous Acid; Phospholipases A2; Rats; Rats, Sprague-Dawley; Time Factors; Transfection