Alpha-ketoisocaproate increases the in vitro P-32 incorporation into intermediate filaments in cerebral cortex of rats

In this study we investigated the effects of alpha -ketaisocaproic (KIC), a lpha -ketoisovaleric (KIV) an alpha -keto-beta -methylvaleric (KMV) acids o n the phosphorylation of intermediate filament (IF) proteins of cerebral co rtex of rats. Tissue slices were incubated with [P-32]orthophosphate in the presence or absence of the acids. The intermediate filament enriched cytos keletal fraction was isolated and the radioactivity incorporated into neuro filament subunits, vimentin and glial fibrillary acidic protein was measure d. Results demonstrated that KIC significantly increased phosphorylation of these proteins whereas the other acids had no effect Experiments using pro tein kinase inhibitors indicated that the effect of KIC was mediated by Ca2 +-calmodulin- and cAMP-dependent protein kinases. This study provides evide nce that KIC, a key metabolite accumulating in maple syrup urine disease, i ncreases phosphorylation of IF proteins. NeuroReport 11:3545-3550 (C) 2000 Lippincott Williams & Wilkins.