Phospholipase A2 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 c14CoS/c14CoS mouse, and in newborn mouse liver--when compared with the cch/cch wild-type--are associated with enhanced levels of reactive oxygenated metabolites (ROMs) and reduced glutathione (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 A2 (PLA2) enzyme activity, 2) Ca2+ dependent Group II secreted PLA2 mRNA levels, 3) arachidonic acid release, and 4) arachidonic acid metabolites co-eluting with prostaglandins D2, E2, and F2 alpha. These findings suggest that the cyclooxygenase-2 (COX2) pathway, and possible involvement of the "inflammatory" and/or "acute phase response" signal transduction pathways, might be activated during the endogenous ROM-mediated oxidative stress response in 14CoS/14CoS cells.
Yu
M
M
University of Cincinnati Medical Center, Ohio 45267-0056, USA.
Jamieson
G A
GA
Leikauf
G D
GD
Nebert
D W
DW
D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000378:metabolism*; D002460:Cell Line; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008555:Melitten / Q000494:pharmacology; D051379:Mice; D008817:Mice, Mutant Strains; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology*; D010741:Phospholipases A / Q000096:biosynthesis*; D054467:Phospholipases A2; D011453:Prostaglandins / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000096:biosynthesis; D015398:Signal Transduction; D014158:Transcription, Genetic
D001095:Arachidonic Acids; D011453:Prostaglandins; D012333:RNA, Messenger; D008555:Melitten; D010741:Phospholipases A; D054467:Phospholipases A2