ToxSci Advance Access originally published online on September 29, 2004
Toxicological Sciences 2005 83(1):89-100; doi:10.1093/toxsci/kfh298
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Toxicological Sciences vol. 83 no. 1 © Society of Toxicology 2005; all rights reserved.
The Effect of a Brominated Flame Retardant, Tetrabromobisphenol-A, on Free Radical Formation in Human Neutrophil Granulocytes: The Involvement of the MAP Kinase Pathway and Protein Kinase C
* Norwegian Defence Research Establishment, Division for Protection, P.O. Box 25, N-2027 Kjeller, Norway, and Norwegian Institute for Air Research, P.O. Box 100, N-2027 Kjeller, Norway
Received July 15, 2004; accepted September 26, 2004
This study investigates the effects of one of the most frequently used brominated flame-retardants (BFR), tetrabromobisphenol-A (TBBPA), on formation of reactive oxygen species (ROS) and calcium levels in human neutrophil granulocytes. TBBPA enhanced ROS production in a concentration-depended manner (1–12 µM), measured as 2,7-dichlorofluorescein diacetate amplified (DCF) fluorescence. The results on ROS production by TBBPA was confirmed by lucigenin-amplified chemiluminescence. The TBBPA induced formation of ROS was due to activation of respiratory burst, as shown by the NADPH oxidase inhibitor DPI (10 µM). TBBPA induced activation of respiratory burst was also inhibited by the MEK 1/2 inhibitor U0126 (10 µM), the PKC inhibitor BIM (0.25 µM), and the tyrosine kinase inhibitor erbstatin-A (25 µM). We also found a small reduction in ROS formation in the absence of extracellular calcium and when verapamil was added. The phosphorylation of ERK 1/2 was confirmed by Western blotting. TBBPA also induced a concentration dependent increase in intracellular free calcium measured with Fura-2/AM. We suggest that exposure of human neutrophil granulocytes to the brominated flame retardant TBBPA leads to an activation of the NADPH oxidase primarily by an ERK 1/2 stimulated pathway. The data also show that PKC, calcium, and tyrosine kinases may be involved in the activation
Key Words: brominated flame-retardants (BFR); tetrabromobisphenol-A; neutrophil granulocytes; reactive oxygen species (ROS); MAP kinase pathway; calcium; extracellular signal-regulated kinase (ERK).
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  T. Reistad, E. Mariussen, A. Ring, and F. Fonnum In Vitro Toxicity of Tetrabromobisphenol-A on Cerebellar Granule Cells: Cell Death, Free Radical Formation, Calcium Influx and Extracellular Glutamate Toxicol. Sci., April 1, 2007; 96(2): 268 - 278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Reistad and E. Mariussen A Commercial Mixture of the Brominated Flame Retardant Pentabrominated Diphenyl Ether (DE-71) Induces Respiratory Burst in Human Neutrophil Granulocytes In Vitro Toxicol. Sci., September 1, 2005; 87(1): 57 - 65. [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]
|
|