title: alpha-Ketoisocaproic acid regulates phosphorylation of intermediate filaments in postnatal rat cortical slices through ionotropic glutamatergic receptors.
abstract: In this study we investigated the effects of alpha-ketoisocaproic acid (KIC), the main keto acid accumulating in the inherited neurometabolic disorder maple syrup urine disease (MSUD), on the in vitro incorporation of 32P into intermediate filament (IF) proteins from cerebral cortex of rats during development. KIC decreased the in vitro incorporation of 32P into the IF proteins studied up to day 12, had no effect on day 15, and increased this phosphorylation in cortical slices of 17- and 21-day-old rats. A similar effect on IF phosphorylation was achieved along development by incubating cortical slices with glutamate. Furthermore, the altered phosphorylation caused by the presence of KIC in the incubation medium was mediated by the ionotropic receptors NMDA, AMPA and kainate up to day 12 and by NMDA and AMPA in tissue slices from 17- and 21-day-old rats. The results suggest that alterations of IF phosphorylation may be associated with the neuropathology of MSUD.
authors.affiliation: Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Rua Ramiro Barcelos 2600 anexo, 90035-003, Porto Alegre, RS, Brazil.
authors.forename: Cláudia
authors.initials: C
authors.lastname: Funchal
authors.forename: Priscila
authors.initials: P
authors.lastname: de Lima Pelaez
authors.forename: Samanta Oliveira
authors.initials: SO
authors.lastname: Loureiro
authors.forename: Lilian
authors.initials: L
authors.lastname: Vivian
authors.forename: Franciele
authors.initials: F
authors.lastname: Dall Bello Pessutto
authors.forename: Lúcia Maria Vieira
authors.initials: LM
authors.lastname: de Almeida
authors.forename: Susana
authors.initials: S
authors.lastname: Tchernin Wofchuk
authors.forename: Moacir
authors.initials: M
authors.lastname: Wajner
authors.forename: Regina
authors.initials: R
authors.lastname: Pessoa Pureur
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D007381:Intermediate Filament Proteins / Q000187:drug effects / Q000378:metabolism; D007382:Intermediate Filaments / Q000187:drug effects* / Q000378:metabolism; D007651:Keto Acids / Q000378:metabolism* / Q000494:pharmacology; D008375:Maple Syrup Urine Disease / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009924:Organ Culture Techniques; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014746:Vimentin / Q000187:drug effects / Q000378:metabolism
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid; D007381:Intermediate Filament Proteins; D007651:Keto Acids; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D014746:Vimentin; C013082:alpha-ketoisocaproic acid