title: Low concentrations of copper in drinking water increase AP-1 binding in the brain.
abstract: Copper (Cu) in trace amounts is essential for biological organisms. However, dysregulation of the redox-active metal has been implicated in different neurological disorders such as Wilson's, Menkes', Alzheimer's, and Parkinson's diseases. Since many households use Cu tubing in the plumbing system, and corrosion causes the metal to leach into the drinking water, there may be adverse effects on the central nervous system connected with low-level chronic exposure. The present study demonstrates that treatment with a biologically relevant concentration of Cu for 3 months significantly increases activation of the redox-modulated transcription factor AP-1 in mouse brains. This was independent of an upstream kinase indicated in AP-1 activation. Another redox-active transcription factor, NF-κB, was not significantly modified by the Cu exposure. These results indicate that the effect of Cu on AP-1 is unique and may involve direct modulation of DNA binding.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA.
authors.forename: Shyang
authors.initials: S
authors.lastname: Lung
authors.affiliation: Center for Occupational and Environmental Health, University of California, Irvine, Irvine, CA, USA.
authors.forename: Huihui
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Occupational and Environmental Health, University of California, Irvine, Irvine, CA, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Bondy
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, Pomona, CA, USA acampbell@westernu.edu.
authors.forename: Arezoo
authors.initials: A
authors.lastname: Campbell
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003300:Copper / Q000506:poisoning*; D019327:Copper Sulfate / Q000008:administration & dosage; D003433:Crosses, Genetic; D004247:DNA / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D020260:Heavy Metal Poisoning, Nervous System / Q000378:metabolism*; D008297:Male; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009994:Osmolar Concentration; D018384:Oxidative Stress; D036401:Toxicity Tests, Chronic; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D014877:Water Pollution, Chemical / Q000009:adverse effects*
chemical_list: D009419:Nerve Tissue Proteins; D018808:Transcription Factor AP-1; D003300:Copper; D004247:DNA; D019327:Copper Sulfate
keywords: AP-1; NF-κB; copper; neurodegenerative diseases; oxidative stress