TY - JOUR
T1 - α-ketoisocaproic acid regulates phosphorylation of intermediate filaments in postnatal rat cortical slices through ionotropic glutamatergic receptors
AU - Funchal, Cláudia
AU - De Lima Pelaez, Priscila
AU - Oliveira Loureiro, Samanta
AU - Vivian, Lilian
AU - Bello Pessutto, Franciele Dall
AU - De Almeida, Lúcia Maria Vieira
AU - Wofchuk, Susana Tchernin
AU - Wajner, Moacir
AU - Pessoa Pureur, Regina
N1 - Funding Information:
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), and Pró-Reitoria de Pesquisa e Pós-Graduação da Universidade Federal do Rio Grande do Sul (PROPESq-UFRGS)
PY - 2002/12/15
Y1 - 2002/12/15
N2 - In this study we investigated the effects of α-ketoisocaproic acid (KIC), the main keto acid 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 rats during development. KIC decreased the in vitro incorporation of 32P into the IF proteins studied up to day 12, had no effect on day 15, and increased this phosphorylation in cortical slices of 17- and 21-day-old rats. A similar effect on IF phosphorylation was achieved along development by incubating cortical slices with glutamate. Furthermore, the altered phosphorylation caused by the presence of KIC in the incubation medium was mediated by the ionotropic receptors NMDA, AMPA and kainate up to day 12 and by NMDA and AMPA in tissue slices from 17- and 21-day-old rats. The results suggest that alterations of IF phosphorylation may be associated with the neuropathology of MSUD.
AB - In this study we investigated the effects of α-ketoisocaproic acid (KIC), the main keto acid 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 rats during development. KIC decreased the in vitro incorporation of 32P into the IF proteins studied up to day 12, had no effect on day 15, and increased this phosphorylation in cortical slices of 17- and 21-day-old rats. A similar effect on IF phosphorylation was achieved along development by incubating cortical slices with glutamate. Furthermore, the altered phosphorylation caused by the presence of KIC in the incubation medium was mediated by the ionotropic receptors NMDA, AMPA and kainate up to day 12 and by NMDA and AMPA in tissue slices from 17- and 21-day-old rats. The results suggest that alterations of IF phosphorylation may be associated with the neuropathology of MSUD.
KW - Cytoskeleton
KW - Development
KW - Glutamatergic receptor
KW - Maple syrup urine disease
KW - Phosphorylation
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U2 - 10.1016/S0165-3806(02)00578-3
DO - 10.1016/S0165-3806(02)00578-3
M3 - Article
C2 - 12480141
AN - SCOPUS:0037115295
SN - 0165-3806
VL - 139
SP - 267
EP - 276
JO - Developmental Brain Research
JF - Developmental Brain Research
IS - 2
ER -