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ToxSci Advance Access published online on October 12, 2009
Toxicological Sciences, doi:10.1093/toxsci/kfp249
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© The Author 2009. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

Decreased expression of the voltage-dependent anion channel in differentiated PC-12 and SH-SY5Y cells following Low-level Pb exposure

John M. Prins, Sunyoung Park and Diana I. Lurie

Center for Structural and Functional Neuroscience, Center for Environmental Health Sciences, Department of Biomedical & Pharmaceutical Sciences, College of Health Professions and Biomedical Sciences, The University of Montana, Missoula, MT 59812

Corresponding Author: Diana I. Lurie, Ph.D., Dept. of Pharmaceutical Sciences, School of Pharmacy and Allied Health Sciences, Skaggs Building Room 383, The University of Montana, Missoula, MT 59812-1552, Phone: 406-243-2103, Fax: 406-243-5228, Email: Diana.lurie{at}umontana.edu

Received August 20, 2009; revision received October 5, 2009; accepted October 6, 2009


  Abstract

Lead (Pb) has been shown to disrupt cellular energy metabolism which may underlie the learning deficits and cognitive dysfunctions associated with environmental Pb exposure. The voltage dependent anion channel (VDAC) plays a central role in regulating energy metabolism in neurons by maintaining cellular ATP levels and regulating calcium buffering, and studies have shown that VDAC expression is associated with learning in mice. In this study, we examined the effect of 5µM and 10µM Pb on VDAC expression in-vitro in order to determine whether Pb alters VDAC expression levels in neuronal cell lines. PC-12 and SH-SY5Y cells were used since they differentiate to resemble primary neuronal cells. VDAC expression levels were significantly decreased 48 h after exposure to Pb in both cell lines. In contrast, exposure to 24 h of hypoxia failed to produce a decrease in VDAC, suggesting that decreased VDAC expression is not a general cellular stress response, but is a result of Pb exposure. This decreased VDAC expression was also correlated with a corresponding decrease in cellular ATP levels. Real-time RT-PCR demonstrated a significant decrease in mRNA levels for the VDAC 1 isoform, indicating that Pb reduces transcription of VDAC1. These results demonstrate that exposure to 5µM and 10µM Pb reducesVDAC transcription and expression and is associated with reduced cellular ATP levels.

Key Words: Voltage Dependent Anion Channel; Lead; energy depression; PC-12 cells; SH-SY5Y cells.


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