Exp Neurobiol.  2012 Mar;21(1):30-36. 10.5607/en.2012.21.1.30.

Effects of Polychlorinated Biphenyls on the Development of Neuronal Cells in Growth Period; Structure-Activity Relationship

• Do Y
• Lee DK

• KMID: 2165388
• DOI: http://doi.org/10.5607/en.2012.21.1.30

Abstract

Polychlorinated biphenyls (PCBs) are accumulated in our body through food chain and cause a variety of adverse health effects including neurotoxicities such as cognitive deficits and motor dysfunction. In particular, neonates are considered as a high risk group for the neurotoxicity of PCBs exposure. The present study attempted to analyze the structure-activity relationship among PCB congeners and the mechanism of PCBs-induced neurotoxicity. We measured total protein kinase C (PKC) activities, PKC isoforms, reactive oxygen species (ROS), and induction of neurogranin (RC-3) and growth associated protein-43 (GAP-43) mRNA in cerebellar granule cells of neonatal rats with phorbol 12, 13-dibutyrate ([3H]PDBu) binding assay, western blot, ROS assay, and reverse transcription PCR (RT-PCR) analysis respectively following the different structural PCBs exposure. Only non-coplanar PCBs showed a significant increase of total PKC-alpha and betaII activity as measured with [3H]PDBu binding assay. ROS were more increased with non-coplanar PCBs than coplanar PCBs. The mRNA levels of RC-3 and GAP-43 were more induced with non-coplanar PCBs than coplanar PCBs, indicating that these factors may be useful biomarkers for differentiating non-coplanar PCBs from coplanar PCBs. Non-coplanar PCBs may be more potent neurotoxic congeners than coplanar PCBs. This study provides evidences that non-coplanar PCBs, which have been neglected in the risk assessment processes, should be added in the future to improve the quality and accuracy of risk assessment on the neuroendocrinal adverse effects of PCBs exposures.

Keyword

neurotoxicity syndrome; polychlorinated biphenyls; structure-activity relationship; protein kinase C; reactive oxygen species; Nerve growth factor

MeSH Terms

Animals
Blotting, Western
Food Chain
GAP-43 Protein
Humans
Infant, Newborn
Nerve Growth Factor
Neurogranin
Neurons
Neurotoxicity Syndromes
Phorbols
Polychlorinated Biphenyls
Polymerase Chain Reaction
Protein Isoforms
Protein Kinase C
Rats
Reactive Oxygen Species
Reverse Transcription
Risk Assessment
RNA, Messenger
Structure-Activity Relationship
Biomarkers
GAP-43 Protein
Nerve Growth Factor
Neurogranin
Phorbols
Polychlorinated Biphenyls
Protein Isoforms
Protein Kinase C
RNA, Messenger
Reactive Oxygen Species