Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

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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.

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.[1]

References

Alpha-keto-beta-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system. Funchal, C., Dall Bello Pessutto, F., de Almeida, L.M., de Lima Pelaez, P., Loureiro, S.O., Vivian, L., Wajner, M., Pessoa-Pureur, R. J. Neurol. Sci. (2004) [Pubmed]

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