Up-regulation of NF-kB-sensitive miRNA-125b and miRNA-146a in metal sulfate-stressed human astroglial (HAG) primary cell cultures

Aileen I. Pogue, Maire E. Percy, Jian Guo Cui, Yuan Yuan Li, S. Bhattacharjee, James M. Hill, Theodore P.A. Kruck, Yuhai Zhao, Walter J. Lukiw

Research output: Contribution to journalArticlepeer-review

61 Scopus citations


Micro RNAs (miRNAs) constitute a unique class of small, non-coding ribonucleic acids (RNAs) that regulate gene expression at the post-transcriptional level. The presence of two inducible miRNAs, miRNA-125b and miRNA-146a, involved in respectively, astroglial cell proliferation and in the innate immune and inflammatory response, is significantly up-regulated in human neurological disorders including Alzheimer's disease (AD). In this study we analyzed abundances miRNA-125b and miRNA-146a in magnesium-, iron-, gallium, and aluminum-sulfate-stressed human-astroglial (HAG) cells, a structural and immune-responsive brain cell type. The combination of iron- plus aluminum-sulfate was found to be significantly synergistic in up-regulating reactive oxygen species (ROS) abundance, NF-kB-DNA binding and miRNA-125b and miRNA-146a expression. Treatment of metal-sulfate stressed HAG cells with the antioxidant phenyl butyl nitrone (PBN) or the NF-kB inhibitors curcumin, the metal chelator-anti-oxidant pyrollidine dithiocarbamate (PDTC), or the resveratrol analog CAY10512, abrogated both NF-kB signaling and induction of these miRNAs. Our observations further illustrate the potential of physiologically relevant amounts of aluminum and iron sulfates to synergistically up-regulate specific miRNAs known to contribute to AD-relevant pathogenetic mechanisms, and suggest that antioxidants or NF-kB inhibitors may be useful to quench metal-sulfate triggered genotoxicity.

Original languageEnglish (US)
Pages (from-to)1434-1437
Number of pages4
JournalJournal of Inorganic Biochemistry
Issue number11
StatePublished - Nov 2011
Externally publishedYes


  • Alzheimer's disease
  • Curcumin
  • Genotoxicity
  • Glial cell proliferation
  • Inflammation
  • Micro RNA (miRNA)
  • Primary human astroglial (HAG) cells
  • Pyrollidine dithiocarbamate (PDTC)
  • Resveratrol analog CAY10512
  • Synaptic deficits

ASJC Scopus subject areas

  • Biochemistry
  • Inorganic Chemistry


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