RRC ID 44247
Author Miyayama T, Arai Y, Suzuki N, Hirano S.
Title Mitochondrial electron transport is inhibited by disappearance of metallothionein in human bronchial epithelial cells following exposure to silver nitrate.
Journal Toxicology
Abstract Silver (Ag) possesses antibacterial activity and has been used in wound dressings and deodorant powders worldwide. However, the metabolic behavior and biological roles of Ag in mammals have not been well characterized. In the present study, we exposed human bronchial epithelial cells (BEAS-2B) to AgNO3 and investigated uptake and intracellular distribution of Ag, expression of metallothionein (MT), generation of reactive oxygen species (ROS), and changes in mitochondrial respiration. The culture medium concentration of Ag decreased with time and stabilized at 12h. The concentration of both Ag and MT in the soluble cellular fraction increased up to 3h and then decreased, indicating that cytosolic Ag relocated to the insoluble fraction of the cells. The levels of mRNAs for the major human MT isoforms MT-I and MT-II paralleled with the protein levels of Ag-MT. The intensity of fluorescence derived from ROS was elevated in the mitochondrial region at 24h. Ag decreased mitochondrial oxygen consumption in a dose-dependent manner and the activity of mitochondrial complex I-IV enzymes was significantly inhibited following exposure to Ag. In a separate experiment, we found that hydrogen peroxide (H2O2) at concentrations as low as 0.001% (equivalent to the concentration of H2O2 in Ag-exposed cells) removed Ag from MT. These results suggest MT was decomposed by cytosolic H2O2, and then Ag released from MT relocated to insoluble cellular fractions and inhibited electron chain transfer of mitochondrial complexes, which eventually led to cell damage.
Volume 305
Pages 20-9
Published 2013-3-8
DOI 10.1016/j.tox.2013.01.004
PII S0300-483X(13)00009-7
PMID 23333424
MeSH Anti-Infective Agents, Local / toxicity* Bronchi / cytology Bronchi / drug effects Bronchi / metabolism* Cell Line Cell Survival / drug effects Copper / metabolism Cytochromes c / metabolism Cytosol / chemistry Cytosol / metabolism Electron Transport / drug effects Electron Transport / physiology* Electron Transport Chain Complex Proteins / metabolism Epithelial Cells / drug effects Epithelial Cells / metabolism* Glutathione / metabolism Humans Hydrogen Peroxide / pharmacology Metallothionein / metabolism* Metallothionein / physiology Mitochondria / drug effects Mitochondria / metabolism* Oxygen Consumption / drug effects Real-Time Polymerase Chain Reaction Silver / metabolism Silver Nitrate / toxicity* Zinc / metabolism
IF 4.099
Times Cited 19
Human and Animal Cells