title: Inhibition of PMCA activity by tau as a function of aging and Alzheimer's neuropathology.
abstract: Ca2+-ATPases are plasma membrane and intracellular membrane transporters that use the energy of ATP hydrolysis to pump cytosolic Ca2+ out of the cell (PMCA) or into internal stores. These pumps are the main high-affinity Ca2+ systems involved in the maintenance of intracellular free Ca2+ at the properly low level in eukaryotic cells. The failure of neurons to keep optimal intracellular Ca2+ concentrations is a common feature of neurodegeneration by aging and aging-linked neuropathologies, such as Alzheimer's disease (AD). This disease is characterized by the accumulation of β-amyloid senile plaques and neurofibrillary tangles of tau, a protein that plays a key role in axonal transport. Here we show a novel inhibition of PMCA activity by tau which is concentration-dependent. The extent of inhibition significantly decreases with aging in mice and control human brain membranes, but inhibition profiles were similar in AD-affected brain membrane preparations, independently of age. No significant changes in PMCA expression and localization with aging or neuropathology were found. These results point out a link between Ca2+-transporters, aging and neurodegeneration mediated by tau protein.
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Avda. de Elvas s/n, 06006 Badajoz, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Berrocal
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Avda. de Elvas s/n, 06006 Badajoz, Spain.
authors.forename: Isaac
authors.initials: I
authors.lastname: Corbacho
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Avda. de Elvas s/n, 06006 Badajoz, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Vázquez-Hernández
authors.affiliation: Centro de Biología Molecular "Severo Ochoa", Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, C/Nicolás Cabrera 1, 28049 Madrid, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ávila
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Avda. de Elvas s/n, 06006 Badajoz, Spain.
authors.forename: M Rosario
authors.initials: MR
authors.lastname: Sepúlveda
authors.affiliation: Departamento de Bioquímica y Biología Molecular y Genética, Facultad de Ciencias, Universidad de Extremadura, Avda. de Elvas s/n, 06006 Badajoz, Spain. Electronic address: anam@unex.es.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Mata
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D051379:Mice; D008875:Middle Aged; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D053499:Plasma Membrane Calcium-Transporting ATPases
keywords: Aging; Alzheimer´s disease; Calcium; PMCA; Tau