TY - JOUR
T1 - Up-regulation of NF-kB-sensitive miRNA-125b and miRNA-146a in metal sulfate-stressed human astroglial (HAG) primary cell cultures
AU - Pogue, Aileen I.
AU - Percy, Maire E.
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.
N1 - Funding Information:
Thanks are extended to Drs. W. Poon, T. Saing and Jian Zhang at brain bank donor institutions. Some of the brain tissues used in these studies were provided by the Memory Impairments and Neurological Disorders (MIND) Institute at the University of California, Irvine Alzheimer's Disease Research Center (UCI-ADRC); funding for the UCI-ADRC was provided by NIH/NIA grant P50 AG16573 . Thanks are extended to Darlene Guillot for expert technical assistance. Part of this study was presented in abstract form at the 9th International Keele meeting on Aluminum 19–23 February 2011 in Niagara-on-the-Lake, Ontario, Canada. These studies were supported in part by a Translational Research Initiative grant from Louisiana State University (WJL), by an Alzheimer Association Investigator-Initiated Research Grant IIRG-09-131729 (WJL) and by NIH NIA AG18031 (WJL).
Copyright:
Copyright 2012 Elsevier B.V., All rights reserved.
PY - 2011/11
Y1 - 2011/11
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Curcumin
KW - Genotoxicity
KW - Glial cell proliferation
KW - Inflammation
KW - Micro RNA (miRNA)
KW - Primary human astroglial (HAG) cells
KW - Pyrollidine dithiocarbamate (PDTC)
KW - Resveratrol analog CAY10512
KW - Synaptic deficits
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U2 - 10.1016/j.jinorgbio.2011.05.012
DO - 10.1016/j.jinorgbio.2011.05.012
M3 - Article
C2 - 22099153
AN - SCOPUS:81855217525
VL - 105
SP - 1434
EP - 1437
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
SN - 0162-0134
IS - 11
ER -
