Artículo de revista
Overexpression of amyloid precursor protein increases copper content in HEK293 cells
Fecha
2009Registro en:
Biochemical and Biophysical Research Communications, Volumen 382, Issue 4, 2018, Pages 740-744
0006291X
10902104
10.1016/j.bbrc.2009.03.096
Autor
Suazo, Miriam
Hodar, Christian
Morgan, Carlos
Cerpa, Waldo
Cambiazo, Verónica
Inestrosa, Nibaldo C.
Gonzalez, Mauricio
Institución
Resumen
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. Cu2+ 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 Cu2+ reduction and 64Cu uptake in two human HEK293 cell lines overexpressing APP. Our results indicate that Cu2+ reduction increased and cells accumulated larger levels of copper, maintaining cell viability at supra-physiological levels of Cu2+ ions. Moreover, wild-type cells exposed to both Cu2+ 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 Cu2+ reductase activity and increased 64Cu uptake. We conclude that Cu2+ reduction activity of APP facilitates cop