Synergistic effects of iron and aluminum on stress-related gene expression in primary human neural cells

Peter N. Alexandrov, Yuhai Zhao, Aileen I. Pogue, Matthew A. Tarr, Theo P.A. Kruck, Maire E. Percy, Jian Guo Cui, Walter J. Lukiw

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

Disturbances in metal-ion transport, homeostasis, overload and metal ion-mediated catalysis are implicated in neurodegenerative conditions such as Alzheimer's disease (AD). The mechanisms of metal-ion induced disruption of genetic function, termed genotoxicity, are not well understood. In these experiments we examined the effects of non-apoptotic concentrations of magnesium-, iron- and aluminum-sulfate on gene expression patterns in untransformed human neural (HN) cells in primary culture using high density DNA array profiling and Western immunoassay. Two week old HN cells were exposed to low micromolar magnesium, iron, or aluminum for 7 days, representing trace metal exposure over one-third of their lifespan. While total RNA yield and abundance were not significantly altered, both iron and aluminum were found to induce HSP27, COX-2, βAPP and DAXX gene expression. Similarly up-regulated gene expression for these stress-sensing, pro-inflammatory and proapoptotic elements have been observed in AD brain. The combination of iron and aluminum together was found to be particularly effective in up-regulating these genes, and was preceded by the evolution of reactive oxygen intermediates as measured by 2′,7′-dichlorofluorescein diacetate assay. These data indicate that physiologically relevant amounts of iron and aluminum are capable of inducing Fenton chemistry-triggered gene expression programs that may support downstream pathogenic responses and brain cell dysfunction.

Original languageEnglish (US)
Pages (from-to)117-127
Number of pages11
JournalJournal of Alzheimer's Disease
Volume8
Issue number2
DOIs
StatePublished - Jan 1 2005

Keywords

  • Aluminum sulfate
  • Alzheimer's disease
  • Apoptosis
  • Fenton chemistry
  • Human neural cells
  • Inflammation
  • Iron sulfate
  • Magnesium sulfate
  • Synergistic effects

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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    Alexandrov, P. N., Zhao, Y., Pogue, A. I., Tarr, M. A., Kruck, T. P. A., Percy, M. E., Cui, J. G., & Lukiw, W. J. (2005). Synergistic effects of iron and aluminum on stress-related gene expression in primary human neural cells. Journal of Alzheimer's Disease, 8(2), 117-127. https://doi.org/10.3233/JAD-2005-8204