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Aspirin prevention of NMDA‐induced neuronal death by direct protein kinase Cζ inhibition
Author(s) -
Crisanti P.,
Leon A.,
Lim D. M.,
Omri B.
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03157.x
Subject(s) - protein kinase c , chemistry , microbiology and biotechnology , protein kinase a , aspirin , nmda receptor , apoptosis , pharmacology , signal transduction , kinase , biochemistry , biology , receptor
Aspirin has been shown to protect against glutamate neurotoxicity via the nuclear factor κB pathway. Some studies have implicated the atypical protein kinase C (PKC) zeta (ζ) isoform in cell protection, but the mechanism involved remains unclear. We show here that aspirin exerts at least some of its effects through PKCζ, decreasing the NMDA‐induced activation, cleavage and nuclear translocation of this molecule. Aspirin (acetylsalicylic acid) directly inhibited the protein kinase activity of PKCζ, whereas salicylic acid did not. This direct effect of aspirin on purified human PKCζ is consistent with PKCζ inhibition preventing the NMDA‐induced death of cortical neurones. Caspase‐3 inhibition blocked the cleavage and nuclear translocation of PKCζ, whereas caspase‐1‐inhibition did not. Thus, PKCζ (protein kinase Mζ) regulates nuclear events essential for the initiation of the apoptotic pathway. Aspirin protects cells against NMDA‐induced apoptosis by means of a novel mechanism targeting PKCζ, a key molecule in inflammatory responses and neurodegeneration.