Korean J Physiol Pharmacol.  2005 Feb;9(1):9-15.

Effects of PCB Congeners in Rodent Neuronal Cells in Culture

• Kim SY
• Yang JH

Abstract

We attempted to analyze the mechanism of polychlorinated biphenyl (PCB) -induced neurotoxicity and identify the target molecules in the neuronal cells for PCBs. Since the developing neuron is particularly sensitive to PCB-induced neurotoxicity, we isolated cerebellar granule cells derived from 7-day old Sprague Dawley (SD) rats and grew cells in culture for additional 7 days to mimic PND-14 conditions. Only non-coplanar PCBs at a high dose showed a significant increase of total protein kinase C (PKC) activity at phobol 12, 13-dibutyrate ([3H]PDBu) binding assay, indicating that non-coplanar PCBs are more neuroactive than coplanar PCBs in neuronal cells. PKC isozymes were immunoblotted with the selected monoclonal antibodies. PKC-alpha, delta, and epsilon were activated with non-coplanar PCB exposure. Receptor for activated C kinase-1 (RACK-1), anchoring protein for activated PKC, was more induced with exposure to coplanar PCBs than non-coplanar PCBs. Reverse transcription PCR (RT-PCR) analysis showed induction of neurogranin (RC-3) and growth associated protein-43 (GAP-43) mRNA with non-coplanar PCBs. The results indicate that these factors may be useful biomarkers for differentiating non-coplanar PCBs from coplanar PCBs. The present study demonstrated that non-coplanar PCBs are more neuroactive congeners than coplanar PCBs.

Keyword

PCB; Neurotoxicity; Structure-activity relation; Cerebellum; Culture; PKC

MeSH Terms

Animals
Antibodies, Monoclonal
Biomarkers
Cerebellum
Isoenzymes
Neurogranin
Neurons*
Polychlorinated Biphenyls
Polymerase Chain Reaction
Protein Kinase C
Rats
Reverse Transcription
RNA, Messenger
Rodentia*
Antibodies, Monoclonal
Isoenzymes
Neurogranin
Polychlorinated Biphenyls
Protein Kinase C
RNA, Messenger