Induction of specific micro RNA (miRNA) species by ROS-generating metal sulfates in primary human brain cells.
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.
Lukiw
Walter J
WJ
Neuroscience Center and Department of Ophthalmology, Louisiana State University Health Sciences Center, New Orleans, LA 70112, USA. wlukiu@lsuhsc.edu
Pogue
Aileen I
AI
D001483:Base Sequence; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008670:Metals / Q000494:pharmacology*; D035683:MicroRNAs / Q000096:biosynthesis*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013431:Sulfates / Q000494:pharmacology*
D008670:Metals; D035683:MicroRNAs; D017382:Reactive Oxygen Species; D013431:Sulfates