title: Overexpression of amyloid precursor protein increases copper content in HEK293 cells.
abstract: Amyloid precursor protein (APP) is a transmembrane glycoprotein widely expressed in mammalian tissues and plays a central role in Alzheimer's disease. However, its physiological function remains elusive. Cu(2+) binding and reduction activities have been described in the extracellular APP135-156 region, which might be relevant for cellular copper uptake and homeostasis. Here, we assessed Cu(2+) reduction and (64)Cu uptake in two human HEK293 cell lines overexpressing APP. Our results indicate that Cu(2+) reduction increased and cells accumulated larger levels of copper, maintaining cell viability at supra-physiological levels of Cu(2+) ions. Moreover, wild-type cells exposed to both Cu(2+) ions and APP135-155 synthetic peptides increased copper reduction and uptake. Complementation of function studies in human APP751 transformed Fre1 defective Saccharomyces cerevisiae cells rescued low Cu(2+) reductase activity and increased (64)Cu uptake. We conclude that Cu(2+) reduction activity of APP facilitates copper uptake and may represent an early step in cellular copper homeostasis.
authors.affiliation: INTA, Laboratorio de Bioinformatica y Expresion Genica, Universidad de Chile, Macul, Santiago, Chile.
authors.forename: Miriam
authors.initials: M
authors.lastname: Suazo
authors.forename: Christian
authors.initials: C
authors.lastname: Hodar
authors.forename: Carlos
authors.initials: C
authors.lastname: Morgan
authors.forename: Waldo
authors.initials: W
authors.lastname: Cerpa
authors.forename: Verónica
authors.initials: V
authors.lastname: Cambiazo
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
authors.forename: Mauricio
authors.initials: M
authors.lastname: Gonzalez