Zinc deficiency increases the susceptibility of human neuroblastoma cells to lead-induced activator protein-1 activation.
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) c-Jun-N-terminal kinase (JNK) and p38 and subsequently activate transcription factor activator protein-1 (AP-1). After 24 h of incubation, 5-50 microM Pb2+ caused a decrease in cell viability that was markedly higher in the Zn-deficient cells compared to controls. Pb caused a time (2-24 h) and dose (5-50 microM)-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.
Department of Nutrition, University of California, Davis, Davis, California 95616, USA.
Lucila
L
Aimo
Patricia I
PI
Oteiza
D001483:Base Sequence; D015153:Blotting, Western; D045744:Cell Line, Tumor; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D017930:Genes, Reporter; D006801:Humans; D007854:Lead / Q000494:pharmacology*; D008156:Luciferases / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015032:Zinc / Q000172:deficiency*
D017931:DNA Primers; D018808:Transcription Factor AP-1; D007854:Lead; D008156:Luciferases; D020928:Mitogen-Activated Protein Kinases; D015032:Zinc