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

作者：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.^*

来源：Journal of Inorganic Biochemistry, 2011, 105(11): 1434-1437.

DOI：10.1016/j.jinorgbio.2011.05.012

• 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

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.

• 出版日期2011-11