Effects of PCB Congeners in Rodent Neuronal Cells in Culture.
- Author:
Sun Young KIM
1
;
Jae Ho YANG
Author Information
1. Department of Pharmacology, School of Medicine, Catholic University of Daegu, Daegu 705-718, Korea. yangjh@cu.ac.kr
- Publication Type:Original Article
- Keywords:
PCB;
Neurotoxicity;
Structure-activity relation;
Cerebellum;
Culture;
PKC
- MeSH:
Animals;
Antibodies, Monoclonal;
Biomarkers;
Cerebellum;
Isoenzymes;
Neurogranin;
Neurons*;
Polychlorinated Biphenyls;
Polymerase Chain Reaction;
Protein Kinase C;
Rats;
Reverse Transcription;
RNA, Messenger;
Rodentia*
- From:The Korean Journal of Physiology and Pharmacology
2005;9(1):9-15
- CountryRepublic of Korea
- Language:English
-
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.
