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ToxSci Advance Access published online on February 16, 2006
Toxicological Sciences, doi:10.1093/toxsci/kfj137
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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
Received January 10, 2006
Accepted February 11, 2006

Neurotoxicology

Zinc Deficiency Increases the Susceptibility of Human Neuroblastoma Cells to Lead-Induced AP-1 Activation

Lucila Aimo 1 and Patricia I. Oteiza 1 *

1 Department of Nutrition, University of California Davis, Davis CA 95616, USA; Department of Environmental Toxicology, University of California Davis, Davis CA 95616, USA

* To whom correspondence should be addressed.
Patricia I. Oteiza, E-mail: poteiza{at}ucdavis.edu


  Abstract

Lead (Pb2+) is a major environmental pollutant that has severe adverse effects on the nervous system. Similar human populations are at risk of suffering both Pb2+ toxicity and zinc (Zn) deficiency. Thus, in the present study we investigated whether Zn deficiency can increase the susceptibility of human neuroblastoma IMR-32 cells to Pb2+-induced oxidative stress which could trigger the activation of the mitogen-activated protein kinases (MAPKs) JNK and p-38 and subsequently activate transcription factor AP-1. After 24 h of incubation, 5-50 µM Pb2+ caused a decrease in cell viability that was markedly lower in the Zn deficient cells compared to controls. Pb caused a time (2-24 h) and dose (5-50 µM)-dependent increase of cell oxidants, with a significantly higher effect in the Zn deficient cells. Pb2+ treatment triggered the activation of JNK and p38, measured as the phosphorylation of JNK and p38, only in cells incubated in the Zn deficient media. The exposure to Pb2+ (2-24 h) led to a higher AP-1-DNA binding activity and AP-1-dependent gene transactivation, only in the Zn deficient cells. Results show that Zn deficiency can increase the cytotoxicity of Pb2+ and the susceptibility of neurons to Pb2+-induced oxidative stress, leading to JNK and p38 phosphorylation and subsequently, AP-1 activation.

Keywords: Lead; Zinc; AP-1; oxidative stress; MAPK.
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