Potentiation of DCA-induced apoptosis by MAPK
inhibition correlates with reduced protein expression of
c-FLIP-L, c-FLIP-S and Bcl-XL and
is blocked by overexpression of c-FLIP-s. Primary rat hepatocytes were
infected with poly-l-lysine–conjugated adenoviruses to
express either c-FLIP-S or a CMV null virus. Twenty-four
hours after infection, cells were treated with DCA (50 μM) and either
vehicle control or PD98059 (50 μM), and the percentage of apoptosis
determined 360 min after addition of H-33342. Data are
the means of three experiments ± SEM. (Inset) DCA increases
protein expression of Bcl-XL, c-FLIP-S, and
c-FLIP-L in primary hepatocytes, which is reduced by MAPK
inhibition. Cells were treated with DCA (50 μM) and either vehicle
control or PD98059 (50 μM), and the protein levels Bcl-XL
and c-FLIP isoforms were determined 120 min after addition. Data are a
representative experiment (n = 3).