p38 MAPK and Ca2+ contribute to hydrogen peroxide-induced increase of permeability in vascular endothelial cells but ERK does not |
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Authors: | Koichi Niwa Osamu Inanami Toshio Ohta Shigeo Ito Takeshi Karino Mikinori Kuwabara |
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Affiliation: | 1. Laboratory of Biofluid Dynamics, Research Institute for Electronic Science, Hokkaido University, West 6, North 12, Kita-ku, Sapporo, 060-0812, Japan;2. Laboratory of Radiation Biology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan;3. Laboratory of Pharmacology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, 060-0818, Japan |
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Abstract: | To examine the involvement of p38 mitogen-activated protein kinase (p38 MAPK) and extra-cellular 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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Keywords: | Ca2+ Endothelial cells ERK Hydrogen peroxide Permeability p38 MAPK |
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