title: Effect of propionic and methylmalonic acids on the high molecular weight neurofilament subunit (NF-H) in rat cerebral cortex.
abstract: Propionic and methylmalonic acidemias are inherited neurometabolic disorders biochemically characterized by tissue accumulation of propionic (PA) and methylmalonic (MMA) acids, respectively. Neurofilaments (NF) are important cytoskeletal proteins and phosphorylation/dephosphorylation of NF is important to stabilize the cytoskeleton. We investigated the effects of PA and MMA on the high molecular weight neurofilament subunit associated with the cytoskeletal fraction of rat cerebral cortex along development. Cortical slices from 9- to 60-day-old rats were incubated with 2.5 mM PA or MMA. The cytoskeletal fraction was extracted and the immunoreactivity for phosphorylated or total NF-H was analyzed by immunoblotting using specific antibodies. Results showed that treatment of tissue slices with the acids induced an increased Triton-insoluble phosphorylated NF-H immunoreactivity in up to 17-day-old rats. Furthermore, treatments significantly increased the total amount of NF-H in 12-day-old rats. These findings indicate that PA and MMA alter the dynamic regulation of NF-H assembly in the cytoskeletal fraction.
authors.affiliation: Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Vivian
authors.forename: F Dall Bello
authors.initials: FD
authors.lastname: Pessutto
authors.forename: L M Vieira
authors.initials: LM
authors.lastname: de Almeida
authors.forename: S de Oliveira
authors.initials: Sde O
authors.lastname: Loureiro
authors.forename: P de Lima
authors.initials: Pde L
authors.lastname: Pelaez
authors.forename: C
authors.initials: C
authors.lastname: Funchal
authors.forename: M
authors.initials: M
authors.lastname: Wajner
authors.forename: R
authors.initials: R
authors.lastname: Pessoa-Pureur
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008764:Methylmalonic Acid / Q000494:pharmacology*; D008970:Molecular Weight; D016900:Neurofilament Proteins / Q000378:metabolism*; D010766:Phosphorylation; D011422:Propionates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016900:Neurofilament Proteins; D011422:Propionates; C051774:neurofilament protein H; D008764:Methylmalonic Acid; C029658:propionic acid