Zinc deficiency increases the susceptibility of human neuroblastoma cells to lead-induced activator protein-1 activation

Lucila Aimo, Patricia I. Oteiza

Research output: Contribution to journalArticle

20 Scopus citations

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 languageEnglish (US)
Pages (from-to)184-191
Number of pages8
JournalToxicological Sciences
Volume91
Issue number1
DOIs
StatePublished - May 2006

Keywords

  • AP-1
  • Lead
  • MAPK
  • Oxidative stress
  • Zinc

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Zinc deficiency increases the susceptibility of human neuroblastoma cells to lead-induced activator protein-1 activation'. Together they form a unique fingerprint.

  • Cite this