Toxicological Sciences 68, 451-457 (2002)
Copyright © 2002 by the Society of Toxicology
NEUROTOXICOLOGY |
Differential Effects of Polybrominated Diphenyl Ethers and Polychlorinated Biphenyls on [3H]Arachidonic Acid Release in Rat Cerebellar Granule Neurons
Cellular and Molecular Toxicology Branch, Neurotoxicology Division, MD 74B, NHEERL, ORD, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711
Polybrominated diphenyl ethers (PBDEs), which are widely used as flame-retardants, have been increasing in environmental and human tissue samples during the past 20–30 years, while other structurally related, persistent organic pollutants such as polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins (on a TEQ basis), have decreased. 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 cause neurotoxic effects, including changes in learning and memory, stimulated the release of [3H]arachidonic acid ([3H]AA) by a cPLA2/iPLA2-dependent mechanism. PLA2(phospholipase A2) 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 was to test whether PBDE mixtures (DE-71 and DE-79), like other organohalogen mixtures, have a similar action on [3H]AA release in an in vitro neuronal culture model. Cerebellar granule cells at 7 days in culture were labeled with [3H]AA for 16–20 h 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 µg/ml, while DE-79, a mostly octabromodiphenyl ether mixture, did not stimulate [3H]AA release, even at 50 µg/ml. The release of [3H]AA by DE-71 is time-dependent, and a significant increase was seen after only 5–10 min of exposure. The removal and chelation of calcium from the exposure buffer, using 0.3 mM EGTA, significantly attenuated the DE-71-stimulated [3H]AA release; however, only an 18% inhibition of the release was demonstrated for the calcium replete conditions at 30 µg/ml DE-71. Methyl arachidonylfluorophosphonate (5 µM), an inhibitor of cPLA2/iPLA2, completely attenuated the DE-71-stimulated [3H]AA release. Further studies focused on comparing the effects of DE-71 with PCB mixtures such as Aroclors 1016 and 1254. Both PCB mixtures stimulated [3H]AA release in a concentration-dependent manner; however, the effect for PCBs was about two times greater than that of the PBDEs on a weight basis, but was comparable on a molar basis. These results indicate that PBDEs stimulated the release of [3H]AA by activating PLA2, which is similar to the effect of other organohalogen mixtures.
Key Words: polybrominated diphenyl ethers; brominated flame retardants; arachidonic acid release; polychlorinated biphenyls; phospholipases; neurotoxicity.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Yu, Y. He, L. W. Y. Yeung, P. K. S. Lam, R. S. S. Wu, and B. Zhou DE-71-Induced Apoptosis Involving Intracellular Calcium and the Bax-Mitochondria-Caspase Protease Pathway in Human Neuroblastoma Cells In Vitro Toxicol. Sci., August 1, 2008; 104(2): 341 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Fischer, A. Fredriksson, and P. Eriksson Coexposure of Neonatal Mice to a Flame Retardant PBDE 99 (2,2',4,4',5-Pentabromodiphenyl Ether) and Methyl Mercury Enhances Developmental Neurotoxic Defects Toxicol. Sci., February 1, 2008; 101(2): 275 - 285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. S. Kodavanti, T. R. Ward, G. Ludewig, L. W. Robertson, and L. S. Birnbaum Polybrominated Diphenyl Ether (PBDE) Effects in Rat Neuronal Cultures: 14C-PBDE Accumulation, Biological Effects, and Structure-Activity Relationships Toxicol. Sci., November 1, 2005; 88(1): 181 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Brant and R. Loch Caruso Late-Gestation Rat Myometrial Cells Express Multiple Isoforms of Phospholipase A2 That Mediate PCB 50-Induced Release of Arachidonic Acid with Coincident Prostaglandin Production Toxicol. Sci., November 1, 2005; 88(1): 222 - 230. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Sanders, L. T. Burka, C. S. Smith, W. Black, R. James, and M. L. Cunningham Differential Expression of CYP1A, 2B, and 3A Genes in the F344 Rat following Exposure to a Polybrominated Diphenyl Ether Mixture or Individual Components Toxicol. Sci., November 1, 2005; 88(1): 127 - 133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. R. S. Kodavanti and T. R. Ward Differential Effects of Commercial Polybrominated Diphenyl Ether and Polychlorinated Biphenyl Mixtures on Intracellular Signaling in Rat Brain in Vitro Toxicol. Sci., June 1, 2005; 85(2): 952 - 962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Bezdecny, R. A. Roth, and P. E. Ganey Effects of 2,2',4,4'-Tetrachlorobiphenyl on Granulocytic HL-60 Cell Function and Expression of Cyclooxygenase-2 Toxicol. Sci., April 1, 2005; 84(2): 328 - 334. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. R. Mundy, T. M. Freudenrich, K. M. Crofton, and M. J. DeVito Accumulation of PBDE-47 in Primary Cultures of Rat Neocortical Cells Toxicol. Sci., November 1, 2004; 82(1): 164 - 169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Siddiqi, R. H. Laessig, and K. D. Reed Polybrominated Diphenyl Ethers (PBDEs): New Pollutants-Old Diseases Clin. Med. Res., October 1, 2003; 1(4): 281 - 290. [Abstract] [Full Text] [PDF]
|
|