title: Influence of chronic ethanol intake on mouse synaptosomal aspartyl aminopeptidase and aminopeptidase A: relationship with oxidative stress indicators.
abstract: Aminopeptidase A (APA) and aspartyl aminopeptidase (ASAP) not only act as neuromodulators in the regional brain renin-angiotensin system, but also release N-terminal acidic amino acids (glutamate and aspartate). The hyperexcitability of amino acid neurotransmitters is responsible for several neurodegenerative processes affecting the central nervous system. The purpose of the present work was to study the influence of chronic ethanol intake, a well known neurotoxic compound, on APA and ASAP activity under resting and K(+)-stimulated conditions at the synapse level. APA and ASAP activity were determined against glutamate- and aspartate-β-naphthylamide respectively in mouse frontal cortex synaptosomes and in their incubation supernatant in a Ca(2+)-containing or Ca(2+)-free artificial cerebrospinal fluid. The neurotoxic effects were analyzed by determining free radical generation, peroxidation of membrane lipids and the oxidation of synaptosomal proteins. In addition, the bioenergetic behavior of synaptosomes was analyzed under different experimental protocols. We obtained several modifications in oxidative stress parameters and a preferential inhibitor effect of chronic ethanol intake on APA and ASAP activities. Although previous in vitro studies failed to show signs of neurodegeneration, these in vivo modifications in oxidative stress parameters do not seem to be related to changes in APA and ASAP, invalidating the idea that an excess of free acidic amino acids released by APA and ASAP induces neurodegeneration.
authors.affiliation: Area de Fisiologia, Departamento de Ciencias de la Salud, Facultad de Ciencias Experimentales y de la Salud de la Universidad de Jaen, Paraje Las Lagunillas s/n 23071, Jaen, Spain. mdmayas@ujaen.es
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Mayas
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Ramírez-Expósito
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: García
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Carrera
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Martínez-Martos
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D000431:Ethanol / Q000494:pharmacology; D043384:Glutamyl Aminopeptidase / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000431:Ethanol; D043384:Glutamyl Aminopeptidase; D011188:Potassium