ToxSci Advance Access originally published online on March 31, 2004
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Toxicological Sciences 80, 54-59 (2004)
Toxicological Sciences vol. 80 no. 1 © Society of Toxicology 2004; all rights reserved.
Ortho-Substituted PCBs Kill Cells by Altering Membrane Structure
,1
* Department of Environmental Health and Toxicology, Department of Biomedical Sciences, School of Public Health, University at Albany, Rensselaer, New York 12144; Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany, New York 12201; and Institute for Health and the Environment, University at Albany, Rensselaer New York 12144
Received November 19, 2003; accepted February 20, 2004
Our previous studies have demonstrated that ortho-substituted PCBs cause a rapid cell death in both thymocytes and cerebellar granule cell neurons, whereas coplanar congeners are without effect at comparable concentrations and exposure times. We have demonstrated that multiple membrane components are altered by these exposures, including the plasma membrane, mitochondria, and endoplasmic reticulum. The present experiments were designed to test the hypothesis that because of their stereochemistry, ortho-substituted congeners cause a greater disruption of membrane integrity than do coplanar congeners, and that this membrane disruption results in altered cellular function and to cell death. To test this hypothesis we have measured fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) in thymocytes, cerebellar granule cells, and lipid bilayer vesicles upon exposure to an ortho-substituted PCB congener (PCB 52) and a coplanar congener (PCB 77), and compared results obtained in these studies to those from flow cytometric studies of plasma membrane permeability to large molecules and elevations of intracellular calcium in living cells. The fluorescence polarization of the DPH probe, which inserts into the lipid bilayer, reflects changes in membrane fluidity. In all three preparations we found that whereas fluorescence polarization was unchanged upon exposure to PCB 77, it was reduced significantly by PCB 52, reflecting an increase in membrane fluidity. These observations are consistent with the hypothesis that ortho-substituted PCBs disrupt membrane structure, which alters the function of membrane proteins. In the two cell types we have studied, the disruption is sufficient to cause death of the cell within a brief time.
Key Words: membrane fluidity; fluorescence polarization; lipid bilayer membranes; thymocytes; cerebellar granule cells.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. G. Coburn, M. C. Curras-Collazo, and P. R. S. Kodavanti Polybrominated Diphenyl Ethers and ortho-Substituted Polychlorinated Biphenyls as Neuroendocrine Disruptors of Vasopressin Release: Effects during Physiological Activation In Vitro and Structure-Activity Relationships Toxicol. Sci., July 1, 2007; 98(1): 178 - 186. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Chung and R. L. Caruso 2,2'-Dichlorobiphenyl Decreases Amplitude and Synchronization of Uterine Contractions Through MAPK1-Mediated Phosphorylation of GJA1 (Connexin43) and Inhibition of Myometrial Gap Junctions Biol Reprod, November 1, 2005; 73(5): 974 - 982. [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]
|
|