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 language | English (US) |
---|---|
Pages (from-to) | 17-24 |
Number of pages | 8 |
Journal | Journal of the Neurological Sciences |
Volume | 217 |
Issue number | 1 |
DOIs | |
State | Published - Jan 15 2004 |
Funding
We thank Dr. Carlos Fernando de Mello for the generous gifting of the GABA antagonists. This work was supported by Conselho Nacional de Desenvolvimento Cientı́fico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nı́vel Superior (CAPES), Financiadora de Estudos e Projetos (FINEP), FAPERGS and Pró-Reitoria de Pesquisa e Pós-Graduação da Universidade Federal do Rio Grande do Sul (PROPESq-UFRGS).
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