Key result
p38 MAPK inhibition blocks H2O2-induced endothelial permeability in vitro, whereas ERK inhibition does not.
Why the study?
The roles of p38 MAPK, ERK, and intracellular Ca2+ in oxidative stress-induced increase of endothelial permeability were unclear.
In bovine pulmonary artery endothelial cells, oxidative stress-induced permeability increases are mediated by p38 MAPK activation and increased intracellular calcium, but not by ERK.
In vitro data on MAPK pathways in endothelial permeability should not guide therapy; leaves open their mechanistic role in oxidative vascular injury.
To examine the involvement of p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-regulated kinase (ERK) in the oxidative stress-induced increase of permeability in endothelial cells, the effects of a p38 MAPK inhibitor (SB203580) and ERK inhibitor (PD90859) on the H2O2-induced increase of permeability in bovine pulmonary artery endothelial cells (BPAEC) were investigated using a two-compartment system partitioned by a semi-permeable filter. H2O2 at 1 mM caused an increase of the permeation rate of fluorescein isothiocyanate (FITC)-labeled dextran 40 through BPAEC monolayers. SB203580 inhibited the H2O2-induced increase of permeability but PD98059 did not, though activation (phosphorylation) of both p38 MAPK and ERK was observed in H2O2-treated cells in Western blot analysis. An H2O2-induced increase of the intracellular Ca2+ concentration ([Ca2+]i) was also observed and an intracellular Ca2+ chelator (BAPTA-AM) significantly inhibited the H2O2-induced increase of permeability. However, it showed no inhibitory effects on the H2O2-induced phosphorylation of p38 MAPK and ERK. The H2O2-induced increase of [Ca2+]i was not influenced by SB203580 and PD98059. These results indicate that the activation of p38 MAPK and the increase of [Ca2+]i are essential for the H2O2-induced increase of endothelial permeability and that ERK is not.
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Niwa et al. (2001) studied Oxidative stress-induced increase of endothelial permeability. p38 MAPK inhibitor (SB203580) and ERK inhibitor (PD90859) was evaluated on H2O2-induced increase of permeability. In bovine pulmonary artery endothelial cells, a p38 MAPK inhibitor (SB203580) inhibited the H2O2-induced increase of permeability, whereas an ERK inhibitor (PD98059) did not.
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