title: Evidence that hyperprolinemia alters glutamatergic homeostasis in rat brain: neuroprotector effect of guanosine.
abstract: This study investigated the effects of acute and chronic hyperprolinemia on glutamate uptake, as well as some mechanisms underlying the proline effects on glutamatergic system in rat cerebral cortex. The protective role of guanosine on effects mediated by proline was also evaluated. Results showed that acute and chronic hyperprolinemia reduced glutamate uptake, Na(+), K(+)-ATPase activity, ATP levels and increased lipoperoxidation. GLAST and GLT-1 immunocontent were increased in acute, but not in chronic hyperprolinemic rats. Our data suggest that the effects of proline on glutamate uptake may be mediated by lipid peroxidation and disruption of Na(+), K(+)-ATPase activity, but not by decreasing in glutamate transporters. This probably induces excitotoxicity and subsequent energy deficit. Guanosine was effective to prevent most of the effects promoted by proline, reinforcing its modulator role in counteracting the glutamate toxicity. However, further studies are needed to assess the modulatory effects of guanosine on experimental hyperprolinemia.
authors.affiliation: Departamento de Bioquímica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600-Anexo, Porto Alegre, RS, CEP 90035-003, Brazil.
authors.forename: Andréa G K
authors.initials: AG
authors.lastname: Ferreira
authors.forename: Aline A
authors.initials: AA
authors.lastname: da Cunha
authors.forename: Emilene B
authors.initials: EB
authors.lastname: Scherer
authors.forename: Fernanda R
authors.initials: FR
authors.lastname: Machado
authors.forename: Maira J
authors.initials: MJ
authors.lastname: da Cunha
authors.forename: Andressa
authors.initials: A
authors.lastname: Braga
authors.forename: Ben Hur
authors.initials: BH
authors.lastname: Mussulini
authors.forename: Júlia D
authors.initials: JD
authors.lastname: Moreira
authors.forename: Susana
authors.initials: S
authors.lastname: Wofchuk
authors.forename: Diogo O
authors.initials: DO
authors.lastname: Souza
authors.forename: Angela T S
authors.initials: AT
authors.lastname: Wyse
mesh_terms: D050842:1-Pyrroline-5-Carboxylate Dehydrogenase / Q000172:deficiency; D000255:Adenosine Triphosphate / Q000378:metabolism; D000592:Amino Acid Metabolism, Inborn Errors / Q000503:physiopathology*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000503:physiopathology*; D018698:Glutamic Acid / Q000378:metabolism*; D006151:Guanosine / Q000494:pharmacology*; D006706:Homeostasis; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011394:Proline Oxidase / Q000172:deficiency; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D017392:Thiobarbituric Acid Reactive Substances; D006151:Guanosine; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D050842:1-Pyrroline-5-Carboxylate Dehydrogenase; D011394:Proline Oxidase; D000254:Sodium-Potassium-Exchanging ATPase