Alpha-keto-beta-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system.
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.
Funchal
Cláudia
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
Franciele
F
de Almeida
Lúcia Maria Vieira
LM
de Lima Pelaez
Priscila
P
Loureiro
Samanta Oliveira
SO
Vivian
Lilian
L
Wajner
Moacir
M
Pessoa-Pureur
Regina
R
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001596:Benzylamines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D045782:Hemiterpenes; D066298:In Vitro Techniques; D007382:Intermediate Filaments / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D007651:Keto Acids / Q000494:pharmacology*; D010759:Phosphorus Isotopes / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011854:Radiochemistry / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology; D014746:Vimentin / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology; D000096926:Benzenesulfonamides
D001596:Benzylamines; D004791:Enzyme Inhibitors; D018756:GABA Antagonists; D005904:Glial Fibrillary Acidic Protein; D045782:Hemiterpenes; D007546:Isoquinolines; D007651:Keto Acids; D010759:Phosphorus Isotopes; D013449:Sulfonamides; D014746:Vimentin; D005680:gamma-Aminobutyric Acid; C072105:KN 93; D000096926:Benzenesulfonamides; C016211:alpha-keto-beta-methylvaleric acid; C001505:alpha-ketoisovalerate; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide