α-Keto-β-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system

Cláudia Funchal; Franciele Dall Bello Pessutto; Lúcia Maria Vieira De Almeida; Priscila De Lima Pelaez; Samanta Oliveira Loureiro; Lilian Vivian; Moacir Wajner; Regina Pessoa-Pureur

doi:10.1016/j.jns.2003.08.003

α-Keto-β-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system

Cláudia Funchal, Franciele Dall Bello Pessutto, Lúcia Maria Vieira De Almeida, Priscila De Lima Pelaez, Samanta Oliveira Loureiro, Lilian Vivian, Moacir Wajner, Regina Pessoa-Pureur^*

^*Corresponding author for this work

Medicine, Rheumatology Division

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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 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.

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	https://doi.org/10.1016/j.jns.2003.08.003
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

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10.1016/j.jns.2003.08.003

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Funchal, C., Dall Bello Pessutto, F., Vieira De Almeida, L. M., De Lima Pelaez, P., Oliveira Loureiro, S., Vivian, L., Wajner, M., & Pessoa-Pureur, R. (2004). α-Keto-β-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. https://doi.org/10.1016/j.jns.2003.08.003

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title = "α-Keto-β-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system",

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.",

keywords = "Gabaergic system, Intermediate filaments, Maple syrup urine disease, Phosphorylation, α-Keto-β-methylvaleric acid, α-Ketoisovaleric acid",

author = "Cl{\'a}udia Funchal and {Dall Bello Pessutto}, Franciele and {Vieira De Almeida}, {L{\'u}cia Maria} and {De Lima Pelaez}, Priscila and {Oliveira Loureiro}, Samanta and Lilian Vivian and Moacir Wajner and Regina Pessoa-Pureur",

note = "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 Tecnol{\'o}gico (CNPq), Coordena{\c c}{\~a}o de Aperfei{\c c}oamento de Pessoal de Nı́vel Superior (CAPES), Financiadora de Estudos e Projetos (FINEP), FAPERGS and Pr{\'o}-Reitoria de Pesquisa e P{\'o}s-Gradua{\c c}{\~a}o da Universidade Federal do Rio Grande do Sul (PROPESq-UFRGS).",

year = "2004",

month = jan,

day = "15",

doi = "10.1016/j.jns.2003.08.003",

language = "English (US)",

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Funchal, C, Dall Bello Pessutto, F, Vieira De Almeida, LM, De Lima Pelaez, P, Oliveira Loureiro, S, Vivian, L, Wajner, M & Pessoa-Pureur, R 2004, 'α-Keto-β-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, pp. 17-24. https://doi.org/10.1016/j.jns.2003.08.003

α-Keto-β-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system. / Funchal, Cláudia; Dall Bello Pessutto, Franciele; Vieira De Almeida, Lúcia Maria et al.
In: Journal of the Neurological Sciences, Vol. 217, No. 1, 15.01.2004, p. 17-24.

Research output: Contribution to journal › Article › peer-review

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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DO - 10.1016/j.jns.2003.08.003

M3 - Article

C2 - 14675604

AN - SCOPUS:0346219384

SN - 0022-510X

VL - 217

SP - 17

EP - 24

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

IS - 1

ER -

α-Keto-β-methylvaleric acid increases the in vitro phosphorylation of intermediate filaments in cerebral cortex of young rats through the gabaergic system

Abstract

Funding

Keywords

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