p38-MAP Kinase Mediates Bax Translocation During Neuronal Apoptosis
Ghatan S., Larner S., Kinoshita Y., Hetman M., Patel
L., Xia Z., Youle R.J. and Morrison R.S. p38 Mitogen-activated Protein Kinase
Mediates Bax translocation and Caspase Induction in Nitric Oxide-induced
Apoptosis in Neurons. J. Cell Biol., 150:335-348, 2000.
Neuronal damage induces p38 MAP kinase-dependent alterations in the intracellular
distribution of the cell death activator, Bax. Neuronal damage
induced by increased levels of nitric oxide (SNP) produced significant
changes in the distribution of the cell death activator, Bax (green fluorescence),
which involved a change from a diffuse, cytosolic distribution (A &
E) to a punctate pattern (B & F) of fluorescence. This change is consistent
with the redistribution of Bax from the cytosol to the mitochondria where
it promotes a decline in mitochondrial integrity and function. Addition
of the p38 MAP kinase inhibitor, SB203580, suppressed Bax translocation
in both SH-SY5Y cells (A-D) and primary cortical neurons (E-G), maintaining
a diffuse cytoplasmic distribution of fluorescence (C & G). A cell
permeable caspase inhibitor, zVAD-fmk (20 µM), had no effect on
Bax translocation induced by SNP exposure (D). Bax translocation was observed
in cells that displayed varying degrees of chromatin condensation and
nuclear fragmentation as depicted by the DNA-binding dye, Hoechst 33342
(purple stain). These results suggest that p38 MAP kinase activity regulates
the translocation of Bax from the cytosol to the mitochondria in response
to nitric oxide-induced damage in neurons.
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