Article

Inhibition of caspase-3 activation by SB 203580, p38 mitogen-activated protein kinase inhibitor in nitric oxide-induced apoptosis of PC-12 cells

Journal of Molecular Neuroscience (impact factor: 2.5). 04/2012; 15(3):243-250. DOI:10.1385/JMN:15:3:243 pp.243-250

ABSTRACT Mitogen-activated protein kinase (MAPK) p38 plays pivotal role in cell proliferation, differentiation, and apoptosis when
cysteine protease caspase induces apoptosis in different cell systems. SB 203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)1
H-imidazole) is widely used as a specific inhibitor of p38 MAPK, and prevents apoptosis induced by various agents. The effect
of SB 203580 on nitric oxide(NO)- or peroxynitrite-induced cell death is not known. Western blotting results indicate that
p38 MAPK was activated significantly in NO- or peroxynitrite-induced cell death in a time-dependent manner, and subsequently
this cell death was markedly inhibited by SB 203580, as determined by fluorescence-activated cell sorting (FACS)-can analyzer.
Furthermore, NO/peroxynitrite-induced caspase-3 activation was notably inhibited by SB 203580, however, phosphorylation of
either p38 MAPK or p44/42 was not influenced by SB 203580. Thus, it is likely that SB 203580 prevents NO/peroxynitrite-induced
cell death by inhibiting caspase-3 activation in PC-12 cells.

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Keywords

apoptosis
 
apoptosis induced
 
cell death
 
cell proliferation
 
cysteine protease caspase induces apoptosis
 
different cell systems
 
FACS)-can analyzer
 
fluorescence-activated cell sorting
 
Mitogen-activated protein kinase
 
nitric oxide(NO)-
 
NO-
 
NO/peroxynitrite-induced caspase-3 activation
 
PC-12 cells
 
peroxynitrite-induced cell death
 
phosphorylation
 
pivotal role
 
various agents
 
Western blotting results