Journal
JOURNAL OF INORGANIC BIOCHEMISTRY
Volume 105, Issue 11, Pages 1434-1437Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2011.05.012
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
Funding
- NIH/NIA [P50 AG16573]
- Louisiana State University
- Alzheimer Association [IIRG-09-131729]
- NIH [NIAAG18031]
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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-kappa B-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-kappa B inhibitors curcumin, the metal chelator-anti-oxidant pyrollidine dithiocarbamate (PDTC), or the resveratrol analog CAY10512, abrogated both NF-kappa B 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-kappa B inhibitors may be useful to quench metal-sulfate triggered genotoxicity. (C) 2011 Elsevier Inc. All rights reserved.
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