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NMDA receptors mediate protective activation of extracellular signal regulated kinase1/2
Author(s) -
Gozdz A.,
Habas A.,
Zielinska M.,
Albrecht J.,
Hetman M.
Publication year - 2003
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 - 10.1046/j.1471-4159.85.s2.6_2.x
Subject(s) - nmda receptor , dna damage , apoptosis , receptor , glutamate receptor , poly adp ribose polymerase , sensitization , programmed cell death , neuroscience , microbiology and biotechnology , extracellular , biology , chemistry , biochemistry , dna , polymerase
Neurons are exposed to damaging stimuli, which can trigger cell death and in consequence neurological disorders. Therefore it is important to define defence mechanisms which can be activated in response to damage to reduce neuronal loss. Here we report that cisplatin (CPDD), a neurotoxic anticancer drug that damages DNA triggered apoptosis in cultured cortical neurons from newborn rats. CPDD also activated ERK1/2 whose inhibition by either pharmacological inhibitors or dominant negative mutants increased apoptotic response. Interestingly, the protective ERK1/2 activation was a result of NMDA receptor sensitization. ERK1/2 mobilization was also dependent on activation of PARP. PARP mediated increase of NMDA receptor activity was not accompanied by ATP depletion. This suggests a novel mechanism of PARP‐mediated NMDA receptor regulation. In summary, our results identify a novel compensatory circuitry to defend CNS neurons against DNA damage.