Lactacystin stimulates arachidonic acid metabolism in rat liver cells: effects of cell density on arachidonic acid release, PGI(2) production and cyclooxygenase activity

Lactacystin, an inhibitor of proteasome activity, amplifies prostaglandin I -2 production by rat liver cells stimulated by 12-0-tetradecanoylphorbol-13 -acetate, transforming growth factor -alpha or interleukin-1. Lactacystin a lso stimulates the cell's release of arachidonic acid (AA) and increases th e cyclooxygenase activity in these cells. In serum deprived cells, the enha nced AA release is reduced, cyclooxygenase activity on exogenous AA is incr eased and endogenous production of prostaglandin I-2 is unchanged. These fi ndings suggest that. in vivo, the ratio of dividing to quiescent cells in a tissue may influence eicosanoid production. The increases in prostaglandin I-2 production, AA release and cyclooxygenase activity on exogenous AA res ulting from the combined lactacystin and 12-0-tetradecanoylphorbol-13-aceta te treatment are inhibited by actinomycin or cycloheximide. (C) 2000 Harcou rt Publishers Ltd.