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ToxSci Advance Access originally published online on November 8, 2006
Toxicological Sciences 2007 95(2):436-442; doi:10.1093/toxsci/kfl163
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© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Lead Exposure: Expression and Activity Levels of Oct-2 in the Developing Rat Brain

Saleh A. Bakheet*, Md. Riyaz Basha*, Hui Cai{dagger} and Nasser H. Zawia*,1

* Neurotoxicology and Epigenomics Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI {dagger} Department of Medicine, Vanderbilt Epidemiology Center and Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN

1 To whom correspondence should be addressed at Neurotoxicology and Epigenomics Laboratory, Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881. Fax: (401) 874-5787. E-mail: nzawia{at}uri.edu.

Received August 23, 2006; accepted October 26, 2006


  Abstract

Lead is a highly neurotoxic metal, and the developing central nervous system is particularly vulnerable to the effects of lead. In this study, transcription factors (TFs) that are altered due to lead exposure were identified using macroarray analysis. Rat pups were lactationally exposed to 0.2% lead acetate from birth through weaning. Changes in the developmental profiles of 30 TFs were screened in hippocampal tissue on postnatal day (PND) 5, 15, and 30. The temporal patterns of some TFs were transiently upregulated or repressed following lead exposure in a stage-specific manner; however, Oct-2, which is involved in the regulation of key developmental processes, exhibited sustained elevations during the entire period of study. Lead-induced elevation of Oct-2 was validated by reverse transcriptase–polymerase chain reaction analysis; however, significant elevation of Oct-2 mRNA expression was detected only on PND 5. The DNA-binding activity and protein levels of Oct-2 were further evaluated and found to be consistently induced on PND 5. The elevations observed in Oct-2 mRNA and protein levels as well as DNA-binding activity on PND 5 suggest that developmental maintenance of Oct-2 DNA binding could be impacted through de novo synthesis. These findings identify Oct-2 as a potential molecular target for Pb and suggest that Oct-2 may be associated with lead-induced disturbances in gene expression.

Key Words: Oct-2; lead; development; brain; macroarray.


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