α-Keto-β-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system

Cláudia Funchal, Franciele Dall Bello Pessutto, Lúcia Maria Vieira De Almeida, Priscila De Lima Pelaez, Samanta Oliveira Loureiro, Lilian Vivian, Moacir Wajner, Regina Pessoa-Pureur*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

In this study we investigated the effects of α-ketoisovaleric (KIV) and α-keto-β-methylvaleric acids (KMV), metabolites 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 young rats during development (9-21 days of age) We observed that KMV significantly increased the in vitro incorporation of 32P into the IF proteins studied in cortical slices of 12-day-old rats through the PKA and PKCaMII, with no alteration at the other ages. In contrast, KIV was ineffective in altering the phosphorylating system associated with IF proteins at all ages examined. A similar effect on IF phosphorylation was achieved by incubating cortical slices with γ-aminobutiric acid (GABA). Furthermore, by using specific GABA antagonists, we verified that KMV induced a stimulatory effect on IF phosphorylation of tissue slices from 12-day-old rats mediated by GABAA and GABAB receptors. In conclusion, our results indicate the involvement of the GABAergic system in the alterations of IF phosphorylation caused by KMV, one of the branched-chain keto acids accumulating in MSUD.

Original languageEnglish (US)
Pages (from-to)17-24
Number of pages8
JournalJournal of the Neurological Sciences
Volume217
Issue number1
DOIs
StatePublished - Jan 15 2004

Keywords

  • Gabaergic system
  • Intermediate filaments
  • Maple syrup urine disease
  • Phosphorylation
  • α-Keto-β-methylvaleric acid
  • α-Ketoisovaleric acid

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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