You are here:
STIMULATION OF [3H] ARACHIDONIC ACID RELEASE IN RAT CEREBELLAR GRANULE NEURONS BY POLYBROMINATED DIPHENYL.
Citation:
DerrYellin, E. C. AND PRS Kodavanti. STIMULATION OF [3H] ARACHIDONIC ACID RELEASE IN RAT CEREBELLAR GRANULE NEURONS BY POLYBROMINATED DIPHENYL. Presented at Society of Toxicology, San Francisco, CA, March 25-29, 2001.
Description:
Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants in electronic equipment, plastics, textiles, and building materials. While the presence of other persistent organic pollutants, such as polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins, have decreased in environmental and human tissue samples, PBDEs have been increasing in the past 20-30 years. PBDEs have been detected in human blood, adipose tissue and breast milk, and developmental and long-term exposure to these contaminants may pose a human health risk, especially to children. Previously, we demonstrated that PCBs, which are neurotoxic, stimulated the release of [3H]arachidonic acid ([3H]AA) by a cPLA2/iPLA2 dependent mechanism. PLA2 activity has been associated with learning and memory, and AA has been identified as a second messenger involved in synaptic plasticity. The objective of the present study is to test whether PBDE mixtures (DE-71 and DE-79) have a similar mode of action. Cerebellar granule cells at seven days in culture were labeled with [3H]AA for 16-20 hours and then exposed in vitro to PBDEs. DE-71, a mostly pentabromodiphenyl ether mixture, significantly stimulated [3H]AA release at concentrations as low as 10 g/ml while DE-79, a mostly octabromodiphenyl ether mixture did not stimulate [3H]AA release even at 30 g/ml. Methyl arachidonylfluorophosphonate (5 M), an inhibitor of cPLA2/iPLA2, significantly attenuated the DE-71-stimulated [3H]AA release. The removal and chelation of calcium from the exposure buffer using 0.3 mM EGTA, also significantly attenuated the DE-71-stimulated [3H]AA release; however only a 30 % inhibition of the release was demonstrated for the calcium replete conditions at 30 g/ml DE-71. These results indicate that PBDEs stimulated the release of [3H]AA by activating PLA2 as do other organohalogen mixtures. (This abstract does not necessarily reflect USEPA policy).