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J Inorg Biochem. 2007 Sep;101(9):1265-9. Epub 2007 Jun 13.

Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells.

Author information

1
Neuroscience Center and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. wlukiu@lsuhsc.edu

Abstract

Iron- and aluminum-sulfate together, at nanomolar concentrations, trigger the production of reactive oxygen species (ROS) in cultures of human brain cells. Previous studies have shown that following ROS induction, a family of pathogenic brain genes that promote inflammatory signalling, cellular apoptosis and brain cell death is significantly over-expressed. Notably, iron- and aluminum-sulfate induce genes in cultured human brain cells that exhibit expression patterns similar to those observed to be up-regulated in moderate- to late-stage Alzheimer's disease (AD). In this study we have extended our investigations to analyze the expression of micro RNA (miRNA) populations in iron- and aluminum-sulfate treated human neural cells in primary culture. The main finding was that these ROS-generating neurotoxic metal sulfates also up-regulate a specific set of miRNAs that includes miR-9, miR-125b and miR-128. Notably, these same miRNAs are up-regulated in AD brain. These findings further support the idea that iron- and aluminum-sulfates induce genotoxicity via a ROS-mediated up-regulation of specific regulatory elements and pathogenic genes that redirect brain cell fate towards progressive dysfunction and apoptotic cell death.

PMID:
17629564
PMCID:
PMC2080079
DOI:
10.1016/j.jinorgbio.2007.06.004
[Indexed for MEDLINE]
Free PMC Article

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