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 journalArticle

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Abstract

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
Pages (from-to)1434-1437
Number of pages4
JournalJournal of Inorganic Biochemistry
Volume105
Issue number11
DOIs
StatePublished - Nov 1 2011

Fingerprint

Primary Cell Culture
NF-kappa B
MicroRNAs
Cell culture
Sulfates
Up-Regulation
Metals
Iron
Alzheimer Disease
Antioxidants
RNA
Gallium
Curcumin
Cell proliferation
Chelating Agents
Nervous System Diseases
Aluminum
Innate Immunity
Oxidants
Gene expression

Keywords

  • 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

Cite this

Up-regulation of NF-kB-sensitive miRNA-125b and miRNA-146a in metal sulfate-stressed human astroglial (HAG) primary cell cultures. / Pogue, Aileen I.; Percy, Maire E.; Cui, Jian Guo; Li, Yuan Yuan; Bhattacharjee, S.; Hill, James M.; Kruck, Theodore P A; Zhao, Yuhai; Lukiw, Walter J.

In: Journal of Inorganic Biochemistry, Vol. 105, No. 11, 01.11.2011, p. 1434-1437.

Research output: Contribution to journalArticle

Pogue, AI, Percy, ME, Cui, JG, Li, YY, Bhattacharjee, S, Hill, JM, Kruck, TPA, Zhao, Y & Lukiw, WJ 2011, 'Up-regulation of NF-kB-sensitive miRNA-125b and miRNA-146a in metal sulfate-stressed human astroglial (HAG) primary cell cultures', Journal of Inorganic Biochemistry, vol. 105, no. 11, pp. 1434-1437. https://doi.org/10.1016/j.jinorgbio.2011.05.012
Pogue, Aileen I. ; Percy, Maire E. ; Cui, Jian Guo ; Li, Yuan Yuan ; Bhattacharjee, S. ; Hill, James M. ; Kruck, Theodore P A ; Zhao, Yuhai ; Lukiw, Walter J. / Up-regulation of NF-kB-sensitive miRNA-125b and miRNA-146a in metal sulfate-stressed human astroglial (HAG) primary cell cultures. In: Journal of Inorganic Biochemistry. 2011 ; Vol. 105, No. 11. pp. 1434-1437.
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AU - Cui, Jian Guo

AU - Li, Yuan Yuan

AU - Bhattacharjee, S.

AU - Hill, James M.

AU - Kruck, Theodore P A

AU - Zhao, Yuhai

AU - Lukiw, Walter J.

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