Role of serine esterase in hydrogen peroxide-mediated activation of phospholipase A2 in rabbit pulmonary arterial smooth muscle cells.

ABSTRACT

Exposure of rabbit pulmonary arterial smooth muscle cells to hydrogen peroxide cause dose-dependent stimulation of [14C] arachidonic acid (AA) release and enhancement of the cell membrane-associated phospholipase A2 activity as well as of the cell membrane-bound serine esterase activity tested against synthetic substrate p-tosyl-L-arginine methyl ester. While pretreatment of cells with serine protease inhibitors, viz. phenyl methyl sulphonyl fluoride, diisopropyl fluorophosphate and alpha-1-proteinase inhibitor, and antioxidant vitamin E prevents H2O2 stimulation of AA release and the cell membrane-bound serine esterase and PLA2 activities, that with actinomycin D and cycloheximide is devoid of any effect on H2O2 caused stimulation of AA release and the smooth muscle cell membrane associated serine esterase and PLA2 activities. Treatment of the smooth muscle cell membrane suspension with the serine protease trypsin markedly stimulates PLA2 activity. These results suggest that on exposure to H2O2 the smooth muscle cell membrane-bound serine esterase plays an important role in stimulating the cell membrane associated PLA2 activity thereby resulting in an increase in AA release.