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Arachidonic acid: A key molecule for astrocyte survival to peroxynitrite
Author(s) -
Palomba Letizia,
Cerioni Liana,
Cantoni Orazio
Publication year - 2009
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.20879
Subject(s) - arachidonic acid , peroxynitrite , astrocyte , biology , phospholipase a2 , microbiology and biotechnology , lipid signaling , microglia , neuroinflammation , biochemistry , mitochondrial permeability transition pore , phospholipase , second messenger system , apoptosis , programmed cell death , signal transduction , superoxide , inflammation , immunology , neuroscience , receptor , enzyme , central nervous system
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. © 2009 Wiley‐Liss, Inc.