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Alpha-keto-beta-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system.
J Neurol Sci. 2004 Jan 15; 217(1):17-24.JN

Abstract

In this study we investigated the effects of alpha-ketoisovaleric (KIV) and alpha-keto-beta-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 gamma-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 GABA(A) and GABA(B) 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.

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Authors+Show Affiliations

Funchal C
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.
Dall Bello Pessutto F
No affiliation info available
de Almeida LM
No affiliation info available
de Lima Pelaez P
No affiliation info available
Loureiro SO
No affiliation info available
Vivian L
No affiliation info available
Wajner M
No affiliation info available
Pessoa-Pureur R
No affiliation info available

MeSH

Age FactorsAnalysis of VarianceAnimalsAnimals, NewbornBenzylaminesCerebral CortexDose-Response Relationship, DrugDrug InteractionsElectrophoresis, Polyacrylamide GelEnzyme InhibitorsGABA AntagonistsGlial Fibrillary Acidic ProteinHemiterpenesIn Vitro TechniquesIntermediate FilamentsIsoquinolinesKeto AcidsPhosphorus IsotopesPhosphorylationRadiochemistryRatsRats, WistarSulfonamidesVimentingamma-Aminobutyric Acid

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14675604

Citation

Funchal, Cláudia, et al. "Alpha-keto-beta-methylvaleric Acid Increases the in Vitro Phosphorylation of Intermediate Filaments in Cerebral Cortex of Young Rats Through the Gabaergic System." Journal of the Neurological Sciences, vol. 217, no. 1, 2004, pp. 17-24.
Funchal C, Dall Bello Pessutto F, de Almeida LM, et al. Alpha-keto-beta-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system. J Neurol Sci. 2004;217(1):17-24.
Funchal, C., Dall Bello Pessutto, F., de Almeida, L. M., de Lima Pelaez, P., Loureiro, S. O., Vivian, L., Wajner, M., & Pessoa-Pureur, R. (2004). Alpha-keto-beta-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system. Journal of the Neurological Sciences, 217(1), 17-24.
Funchal C, et al. Alpha-keto-beta-methylvaleric Acid Increases the in Vitro Phosphorylation of Intermediate Filaments in Cerebral Cortex of Young Rats Through the Gabaergic System. J Neurol Sci. 2004 Jan 15;217(1):17-24. PubMed PMID: 14675604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Alpha-keto-beta-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 - de Almeida,Lúcia Maria Vieira, AU - de Lima Pelaez,Priscila, AU - Loureiro,Samanta Oliveira, AU - Vivian,Lilian, AU - Wajner,Moacir, AU - Pessoa-Pureur,Regina, PY - 2003/12/17/pubmed PY - 2004/3/9/medline PY - 2003/12/17/entrez SP - 17 EP - 24 JF - Journal of the neurological sciences JO - J Neurol Sci VL - 217 IS - 1 N2 - In this study we investigated the effects of alpha-ketoisovaleric (KIV) and alpha-keto-beta-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 gamma-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 GABA(A) and GABA(B) 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. SN - 0022-510X UR - https://www.unboundmedicine.com/medline/citation/14675604/Alpha_keto_beta_methylvaleric_acid_increases_the_in_vitro_phosphorylation_of_intermediate_filaments_in_cerebral_cortex_of_young_rats_through_the_gabaergic_system_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022510X03002405 DB - PRIME DP - Unbound Medicine ER -