PHOSPHOLIPASE A(2) ACTIVATION AND INCREASES IN SPECIFIC PROSTAGLANDINS IN THE OXIDATIVELY STRESSED 14COS 14COS MOUSE HEPATOCYTE LINE/

This laboratory has previously shown that increases in the expression of several genes in SV40-transformed hepatocyte cultures derived from the untreated newborn C-14CoS/c(14CoS) and in mouse, newborn mouse liv er-when compared with the c(ch)/c(ch) wild-type-are associated with en hanced levels of reactive oxygenated metabolites (ROMs) and reduced gl utathione (GSH). We show here that, in contrast to the ch/ch wild-type levels, the oxidatively stressed 14CoS/14CoS liver cell line displays 2- to 5-fold increases in: 1) phospholipase A(2) (PLA(2)) enzyme acti vity, 2) Ca2+-dependent Group II secreted PLA(2) mRNA levels, 3) arach idonic acid release, and 4) arachidonic acid metabolites co-eluting wi th prostaglandins D-2, E-2, and F-2 alpha. These findings suggest that the cyclooxygenase-2 (COX2) pathway, and possible involvement of the ''inflammatory'' and/or ''acute phase response'' signal transduction p athways, might be activated during the endogenous ROM-mediated oxidati ve stress response in 14CoS/14CoS cells. (C) 1998 Elsevier Science Inc .