alpha-Ketoisocaproic acid regulates phosphorylation of intermediate filaments in postnatal rat cortical slices through ionotropic glutamatergic receptors.

Abstract

In this study we investigated the effects of alpha-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.

• Authors: Cláudia Funchal, Priscila de Lima Pelaez, Samanta Oliveira Loureiro, Lilian Vivian, Franciele Dall Bello Pessutto, Lúcia Maria Vieira de Almeida, Susana Tchernin Wofchuk, Moacir Wajner, Regina Pessoa Pureur
• Journal: Brain research. Developmental brain research (Brain Res Dev Brain Res) Vol. 139 Issue 2 Pg. 267-76 (Dec 15 2002) ISSN: 0165-3806 [Print] Netherlands
• PMID: 12480141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists
• Glial Fibrillary Acidic Protein
• Intermediate Filament Proteins
• Keto Acids
• Receptors, AMPA
• Receptors, Glutamate
• Receptors, Kainic Acid
• Receptors, Metabotropic Glutamate
• Receptors, N-Methyl-D-Aspartate
• Vimentin
• Glutamic Acid
• alpha-ketoisocaproic acid

Topics

• Animals
• Animals, Newborn
• Cerebral Cortex (drug effects, growth & development, metabolism)
• Excitatory Amino Acid Agonists (pharmacology)
• Excitatory Amino Acid Antagonists (pharmacology)
• Glial Fibrillary Acidic Protein (drug effects, metabolism)
• Glutamic Acid (metabolism, pharmacology)
• Intermediate Filament Proteins (drug effects, metabolism)
• Intermediate Filaments (drug effects, metabolism)
• Keto Acids (metabolism, pharmacology)
• Maple Syrup Urine Disease (metabolism, physiopathology)
• Neurons (drug effects, metabolism)
• Organ Culture Techniques
• Phosphorylation (drug effects)
• Rats
• Rats, Wistar
• Receptors, AMPA (drug effects, metabolism)
• Receptors, Glutamate (drug effects, metabolism)
• Receptors, Kainic Acid (drug effects, metabolism)
• Receptors, Metabotropic Glutamate (drug effects, metabolism)
• Receptors, N-Methyl-D-Aspartate (drug effects, metabolism)
• Synaptic Transmission (drug effects, physiology)
• Vimentin (drug effects, metabolism)