How protein kinase C activation protects nerve cells from oxidative stress-induced cell death

Authors
Citation
P. Maher, How protein kinase C activation protects nerve cells from oxidative stress-induced cell death, J NEUROSC, 21(9), 2001, pp. 2929-2938
Citations number
82
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
21
Issue
9
Year of publication
2001
Pages
2929 - 2938
Database
ISI
SICI code
0270-6474(20010501)21:9<2929:HPKCAP>2.0.ZU;2-S
Abstract
Oxidative stress is implicated in the nerve cell death that occurs in a var iety of neurological disorders, and the loss of protein kinase C (PKC) acti vity has been coupled to the severity of the damage. The functional relatio nship between stress, PKC, and cell death is, however, unknown. Using an im mortalized hippocampal cell line that is particularly sensitive to oxidativ e stress, I show that activation of PKC by the phorbol ester tetradecanoylp horbol acetate (TPA) inhibits cell death via the stimulation of a complex p rotein phosphorylation pathway. TPA treatment leads to the rapid activation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kina se (JNK), the inactivation of p38 mitogen-activated protein kinase (MAPK), and the downregulation of PKC delta. Inhibition of either ERK or JNK activa tion blocks TPA-mediated protection, whereas p38 MAPK and PKC delta inhibit ors block stress-induced nerve cell death. Both p38 MAPK inactivation and J NK activation appear to be downstream of ERK because an agent that blocks E RK activation also blocks the modulation of these other MAP kinase family m embers by TPA treatment. Thus, the protection from oxidative stress afforde d nerve cells by PKC activity requires the combined modulation of multiple enzyme pathways and suggests why the loss of PKC activity contributes to ne rve cell death.