Aspirin prevention of NMDA-induced neuronal death by direct protein kinase Cζ inhibition
| Autor: | D. M. Lim, P. Crisanti, B. Omri, A. Leon |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
0303 health sciences
Programmed cell death biology Neurodegeneration medicine.disease Biochemistry Neuroprotection 3. Good health Cell biology 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Apoptosis medicine biology.protein Nuclear protein Protein kinase A 030217 neurology & neurosurgery Protein kinase C Caspase 030304 developmental biology |
| Zdroj: | Journal of Neurochemistry. 93:1587-1593 |
| ISSN: | 1471-4159 0022-3042 |
| DOI: | 10.1111/j.1471-4159.2005.03157.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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