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The cellular and Genomic response of rat dopaminergic neurons (N27) to coated nanosilver
Chorley, B., W. Ward, Steve Simmons, B. Vallanat, AND B. Veronesi. The cellular and Genomic response of rat dopaminergic neurons (N27) to coated nanosilver. NEUROTOXICOLOGY. Elsevier B.V., Amsterdam, Netherlands, 45:12-21, (2014).
Research examines the neurotoxic potential of nanosilver that has shown ability to transcytose the blood brain barrier
This study examined if nanosilver (nanoAg) of different sizes and coatings were differentially toxic to oxidative stress-sensitive neurons. N27 rat dopaminergic neurons were exposed (0.5-5ppm) to a set of nanoAg of different sizes (10nm, 75nm) and coatings (PVP, citrate) and their physicochemical, cellular and genomic response measured. Both coatings retained their manufactured sizes in culture media, however, the zeta potentials of both sizes of PVP-coated nanoAg were significantly less electronegative than those of their citrate-coated counterparts. Markers of oxidative stress, measured at 0.5-5ppm exposure concentrations, indicated that caspase 3/7 activity and glutathione levels were significantly increased by both sizes of PVP coated nanoAg and by the 75nm citrate-coated nanoAg. Both sizes of PVP-coated na.noAg also increased intra-neuronal nitrite levels and activated ARE/NRF2, a reporter gene for the oxidative stress-protection pathway. Global gene expression on N27 neurons, exposed to 0.5ppm for 8h, indicated a dominant effect by PVP-coated nanoAg over citrate. The 75nm PVP-coated material altered 196 genes that were loosely associated with mitochondrialdysfunction. In contrast, the 10nm PVP-coated nanoAg altered 82 genes that were strongly associated with NRF2 oxidative stress pathways. Less that 20% of the affected genes were shared by both sizes of PVP-coated nanoAg. These cellular and genomic findings suggest that PVP-coated nanoAg is more bioactive than citrate-coated nanoAg. Although both sizes of PVP-coated nanoAg altered the genomic expression of N27 neurons along oxidative stress pathways, exposure to the 75nm nanoAg favored pathways associated with mitochondrial dysfunction, whereas the 1Onm PVP coated nanoAg affected NRF2 neuronal protective pathways.
Record Details:Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY
INTEGRATED SYSTEMS TOXICOLOGY DIVISION
SYSTEMS BIOLOGY BRANCH