US EPA

2155183 

Journal Article 

Abstract 

PCB 50-and TNF alpha-induced release of arachidonic acid and prostaglandins from late gestation rat amnion fibroblast cells is associated with increased expression of calcium independent phospholipase A(2) 

Brant, KA; Caruso, RL; Flatley, EM 

2005 

Yes 

Biology of Reproduction
ISSN: 0006-3363
EISSN: 1529-7268 

73 

Special Issue 

133 

English 

WOS:000230556300290 

Phospholipase A2 (PLA2) enzymes catalyze the rate and #150;limiting step in prostaglandin production by liberating arachidonic acid from membrane phospholipids. Amniotic prostaglandin and arachidonic acid levels are elevated at the time of parturition. Previous reports have shown that polychlorinated biphenyls (PCBs) activate PLA2 to release arachidonic acid from membrane phospholipids. To determine if the amnion can serve as a target for PCB toxicity, gestation day 20 rat amnion fibroblast cells were labeled with 0.5 uCi 3H and #150;arachidonic acid prior to a 4 h exposure to 0 uM (0.1 % DMSO, solvent control) or 50 uM PCB 50, or 100 ng/mL TNFalpha (positive control). PCB 50 and TNFalpha induced a significant release of 3H and #150;arachidonic acid from amnion fibroblast cells (p<0.05), an effect that was associated with a significant increase in calcium independent PLA2 (iPLA2) expression as revealed by western blot analysis (p<0.05). Expression of calcium dependent cPLA2 was increased following a 4 h exposure to TNFalpha (p<0.05), but not PCB 50. Both PCB 50 and TNFalpha induced the release of prostaglandins after 4 h with no significant effect on COX and #150;2, indicating that prostaglandin production was dependent on increased availability of the arachidonic acid substrate. These data suggest that changes in iPLA2 expression may mediate stimulus and #150;induced release of arachidonic acid and prostaglandin production in rat amnion fibroblasts, and that amnion can serve as a target for PCB 50 toxicity.