ToxSci Advance Access published online on January 6, 2007
Toxicological Sciences, doi:10.1093/toxsci/kfl198
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
In Vitro Toxicity of Tetrabromobisphenol-A (TBBPA) on Cerebellar Granule Cells: Cell Death, Free Radical Formation, Calcium Influx and Extracellular Glutamate
TBBPA AND CEREBELLAR GRANULE CELLS IN VITRO
1 Norwegian Defence Research Establishment, Division for Protection, P. O. Box 25, N-2027 Kjeller, Norway 2 Norwegian Institute for Air Research, P. O. Box 100, N-2027 Kjeller, Norway 3 Department of Biochemistry, Institute of Basic Medical Science, University of Oslo, P. O. Box 1112, Blindern, N-0317 Oslo, Norway
Correspondence: Trine Reistad Norwegian Defence Research Establishment, Division for Protection, P. O. Box 25, N-2027 Kjeller, Norway, Phone: + 47 63807824, Fax: + 47 63807509, Email: Trine.Reistad{at}ffi.no
Received November 7, 2006; accepted December 20, 2006
 |
Abstract |
|---|
Tetrabromobisphenol-A (TBBPA) is one of the worlds most widely used brominated flame retardant (BFR). The present study reports effects of TBBPA on primary cultures of cerebellar granule cells (CGC). Using the trypan blue exclusion assay we show that TBBPA induces death of CGC at low micro molar concentrations. Cell death was reduced by the NMDA receptor antagonist MK-801 (3 µM), the antioxidant vitamin E (50 µM), and in calcium free buffer. We further demonstrate that TBBPA's toxicity was accompanied by apoptosis-like nuclear shrinkage, chromatin condensation and DNA fragmentation. Other hallmarks of apoptosis, such as caspase activity were, however, absent, indicating an atypical form of apoptosis. TBBPA increased intracellular free calcium in a concentration-dependent manner. TBBPA also induced an increase in extracellular glutamate in a time-dependent manner. TBBPA gave a concentration-dependent increase in ROS formation measured with DCFH-DA. The ROS formation was inhibited by the extracellular signal regulated protein kinase (ERK) inhibitor U0126 (10 µM), the tyrosine kinase inhibitor erbstatin-A (25 µM), eliminating calcium from the buffer and by the superoxide dismutase inhibitor diethyldithio-carbamic acid (DDC, 100 µM). Further analysis with western blot confirmed phosphorylation of ERK 1/2 after exposure to TBBPA. We found that TBBPA induces ROS formation, increases intracellular calcium, extracellular glutamate and death of CGC in vitro at concentrations comparable to those of PCB. These findings implicate TBBPA as a predicted environmental toxin and bring out the importance of awareness of its hazardous effects.
Key Words: Tetrabromobisphenol-A (TBBPA); cerebellar granule cells (CGC); reactive oxygen species (ROS); cell death; glutamate and calcium.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. Stavenes Andersen, O. A. Voie, F. Fonnum, and E. Mariussen Effects of Methyl Mercury in Combination with Polychlorinated Biphenyls and Brominated Flame Retardants on the Uptake of Glutamate in Rat Brain Synaptosomes: A Mathematical Approach for the Study of Mixtures Toxicol. Sci., November 1, 2009; 112(1): 175 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|