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Effects of polychlorinated biphenyls on the development of neuronal cells in growth period; structure-activity relationship.

Do Y, Lee DK - Exp Neurobiol (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Catholic University of Daegu School of Medicine, Daegu 705-718, Korea.

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 ([(3)H]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-α and βII activity as measured with [(3)H]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.

No MeSH data available.


Related in: MedlinePlus

Translocation of cerebellar PKC isoforms from the cytosol to the membrane following PCBs exposure (50 µM) with western blot. (A) PKC-α made no apparent migration in PCB 126 or PCB 169 but made apparent migration from cytosol to membrane in PCB 4 and Aroclor 1256. (B) Since similar observation was made from PKC-βII, non-coplanar PCBs exerted greater effects on neuronal cells.*Significantly different from control at p<0.05.
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Figure 2: Translocation of cerebellar PKC isoforms from the cytosol to the membrane following PCBs exposure (50 µM) with western blot. (A) PKC-α made no apparent migration in PCB 126 or PCB 169 but made apparent migration from cytosol to membrane in PCB 4 and Aroclor 1256. (B) Since similar observation was made from PKC-βII, non-coplanar PCBs exerted greater effects on neuronal cells.*Significantly different from control at p<0.05.

Mentions: When general activity of PKC was analyzed using [3H]PDBu, non-coplanar PCBs were found to be more active than coplanar PCBs (Table 2). While PCB 126 and PCB 169 in the coplanar structure showed no remarkable change even at 50 µM, PCB 4 in the non-coplanar structure had binding increased by approximately 1.5 times. The commercial mixture containing a large amount of non-coplanar PCBs, Aroclor 1256, also showed the same level of increase in binding to PCB 4. It was therefore suggested that PCB causing PKC activity within neuronal cells had a significant non-coplanar structure. When PKC congeners playing an important role for the signaling system were analyzed with western blot, PKC-α made no apparent migration in PCB 126 or PCB 169 but made apparent migration from cytosol to membrane in PCB 4 and Aroclor 1256 (Fig. 2A). Similar observations were made from PKC-βII (Fig. 2B).


Effects of polychlorinated biphenyls on the development of neuronal cells in growth period; structure-activity relationship.

Do Y, Lee DK - Exp Neurobiol (2012)

Translocation of cerebellar PKC isoforms from the cytosol to the membrane following PCBs exposure (50 µM) with western blot. (A) PKC-α made no apparent migration in PCB 126 or PCB 169 but made apparent migration from cytosol to membrane in PCB 4 and Aroclor 1256. (B) Since similar observation was made from PKC-βII, non-coplanar PCBs exerted greater effects on neuronal cells.*Significantly different from control at p<0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3294071&req=5

Figure 2: Translocation of cerebellar PKC isoforms from the cytosol to the membrane following PCBs exposure (50 µM) with western blot. (A) PKC-α made no apparent migration in PCB 126 or PCB 169 but made apparent migration from cytosol to membrane in PCB 4 and Aroclor 1256. (B) Since similar observation was made from PKC-βII, non-coplanar PCBs exerted greater effects on neuronal cells.*Significantly different from control at p<0.05.
Mentions: When general activity of PKC was analyzed using [3H]PDBu, non-coplanar PCBs were found to be more active than coplanar PCBs (Table 2). While PCB 126 and PCB 169 in the coplanar structure showed no remarkable change even at 50 µM, PCB 4 in the non-coplanar structure had binding increased by approximately 1.5 times. The commercial mixture containing a large amount of non-coplanar PCBs, Aroclor 1256, also showed the same level of increase in binding to PCB 4. It was therefore suggested that PCB causing PKC activity within neuronal cells had a significant non-coplanar structure. When PKC congeners playing an important role for the signaling system were analyzed with western blot, PKC-α made no apparent migration in PCB 126 or PCB 169 but made apparent migration from cytosol to membrane in PCB 4 and Aroclor 1256 (Fig. 2A). Similar observations were made from PKC-βII (Fig. 2B).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, Catholic University of Daegu School of Medicine, Daegu 705-718, Korea.

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 ([(3)H]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-α and βII activity as measured with [(3)H]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.

No MeSH data available.


Related in: MedlinePlus