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POSSIBLE MOLECULAR TARGETS OF HALOGENATED ARMOATIC HYDROCARBONS IN NEURONAL CELLS.
Citation:
Yang, J. H. AND PRS Kodavanti. POSSIBLE MOLECULAR TARGETS OF HALOGENATED ARMOATIC HYDROCARBONS IN NEURONAL CELLS. Presented at Society of Toxicology, San Francisco, CA, March 25-29, 2001.
Description:
Halogenated aromatic hydrocarbons including polychlorinated biphenyls (PCBs) are persistent bioaccumulative toxicants. Due to these characteristics, there is considerable regulatory concern over the potential adverse health affects, especially to children, associated with exposure to these chemicals. Although health effects including motor dysfunction and impairments in learning and memory have been identified, their molecular sites of action are unknown. Previous studies from this laboratory demonstrated that, while ortho PCBs perturbed intracellular signaling mechanisms including protein kinase C (PKC) translocation, non-ortho PCBs did not. Since PKC is implicated in the modulation of motor behavior as well as learning and memory and the roles of PKC are isozyme-specific, we have now studied the effects of two structurally distinct PCBs on isozymes of PKC in cerebellar granule cell culture model. Cells were exposed to 2,2'-dichlorobiphenyl (ortho-PCB; 2,2'-DCB) or 4,4'-dichlorobiphenyl (non-ortho PCB; 4,4'-DCB) for 15 min, respectively, and were subsequently fractionated and immunoblotted against the selected PKC isozyme monoclonal antibodies ( , , , , , ). While 2,2'-DCB induced a translocation of PKC- [cytosol (%of control): 54 +12 at 25 ?M and 66 + 10 at 50 ?M; membrane (% of control): 186 + 37 at 25 ?M and 200 + 48 at 50 ?M] and - [cytosol (% of control): 92 + 12 at 25 ?M and 97 + 15 at 50 ?M; membrane (% of control): 143 + 23 at 25 ?M and 192 + 24 at 50 ?M] from cytosol to membrane fraction, 4,4'-DCB had no effect. The expression of PKC- in these cells was below the detectible level. PKC- , - and - were present in these cells, but were not altered by PCB exposure. These results suggest that the effects of 2,2'-DCB on PKC is isozyme-dependent and PKC- as well as - may be target molecules for ortho-PCBs in neuronal cells. (This abstract does not necessarily reflect USEPA policy).