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 language | English |
|---|---|
| Pages (from-to) | 1434-1437 |
| Number of pages | 4 |
| Journal | Journal of Inorganic Biochemistry |
| Volume | 105 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2011 |
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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 journal › Article
}
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.
PY - 2011/11/1
Y1 - 2011/11/1
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
UR - http://www.scopus.com/inward/record.url?scp=81855217525&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=81855217525&partnerID=8YFLogxK
U2 - 10.1016/j.jinorgbio.2011.05.012
DO - 10.1016/j.jinorgbio.2011.05.012
M3 - Article
VL - 105
SP - 1434
EP - 1437
JO - Journal of Inorganic Biochemistry
JF - Journal of Inorganic Biochemistry
SN - 0162-0134
IS - 11
ER -