TY - JOUR
T1 - α-Keto-β-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system
AU - Funchal, Cláudia
AU - Dall Bello Pessutto, Franciele
AU - Vieira De Almeida, Lúcia Maria
AU - De Lima Pelaez, Priscila
AU - Oliveira Loureiro, Samanta
AU - Vivian, Lilian
AU - Wajner, Moacir
AU - Pessoa-Pureur, Regina
N1 - Funding Information:
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).
PY - 2004/1/15
Y1 - 2004/1/15
N2 - 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.
AB - 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.
KW - Gabaergic system
KW - Intermediate filaments
KW - Maple syrup urine disease
KW - Phosphorylation
KW - α-Keto-β-methylvaleric acid
KW - α-Ketoisovaleric acid
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U2 - 10.1016/j.jns.2003.08.003
DO - 10.1016/j.jns.2003.08.003
M3 - Article
C2 - 14675604
AN - SCOPUS:0346219384
VL - 217
SP - 17
EP - 24
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
SN - 0022-510X
IS - 1
ER -