title: Ethylmalonic acid modulates Na+, K(+)-ATPase activity and mRNA levels in rat cerebral cortex.
abstract: Ethylmalonic acid (EMA) accumulates in tissues of patients affected by short-chain acyl-CoA dehydrogenase deficiency and ethylmalonic encephalopathy, illnesses characterized by variable neurological symptoms. In this work, we investigated the in vitro and in vivo EMA effects on Na(+), K(+)-ATPase (NAK) activity and mRNA levels in cerebral cortex from 30-day-old rats. For in vitro studies, cerebral cortex homogenates were incubated in the presence of EMA at 0.5, 1, or 2.5 mM concentrations for 1 h. For in vivo experiments, animals received three subcutaneous EMA injections (6 μmol g(-1); 90-min interval) and were killed 60 min after the last injection. After that, NAK activity and its mRNA expression were measured. We observed that EMA did not affect this enzyme activity in vitro. In contrast, EMA administration significantly increased NAK activity and decreased mRNA NAK expression as assessed by semiquantitative reverse transcriptase polymerase chain reaction when compared with control group. Considering the high score of residues prone to phosphorylation on NAK, this profile can be associated with a possible regulation by specific phosphorylation sites of the enzyme. Altogether, the present results suggest that NAK alterations may be involved in the pathophysiology of brain damage found in patients in which EMA accumulates.
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Programa de Pós-graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil. patricia.schuck@pq.cnpq.br
authors.forename: Patrícia Fernanda
authors.initials: PF
authors.lastname: Schuck
authors.forename: Dênis Reis
authors.initials: DR
authors.lastname: De Assis
authors.forename: Carolina Maso
authors.initials: CM
authors.lastname: Viegas
authors.forename: Talita Carneiro Brandão
authors.initials: TC
authors.lastname: Pereira
authors.forename: Jéssica Luca
authors.initials: JL
authors.lastname: Machado
authors.forename: Camila Brulezi
authors.initials: CB
authors.lastname: Furlanetto
authors.forename: Mauricio Reis
authors.initials: MR
authors.lastname: Bogo
authors.forename: Emilio Luiz
authors.initials: EL
authors.lastname: Streck
authors.forename: Gustavo Costa
authors.initials: GC
authors.lastname: Ferreira
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D008314:Malonates / Q000494:pharmacology*; D010766:Phosphorylation; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D008314:Malonates; D012333:RNA, Messenger; C038080:ethylmalonic acid; D000254:Sodium-Potassium-Exchanging ATPase