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) c-Jun-N-terminal kinase (JNK) and p38 and subsequently activate transcription factor activator protein-1 (AP-1). After 24 h of incubation, 5-50μM 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 (5-50μM)-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.
Original language | English (US) |
---|---|
Pages (from-to) | 184-191 |
Number of pages | 8 |
Journal | Toxicological Sciences |
Volume | 91 |
Issue number | 1 |
DOIs | |
State | Published - May 2006 |
Keywords
- AP-1
- Lead
- MAPK
- Oxidative stress
- Zinc
ASJC Scopus subject areas
- Toxicology