ArticleNeurochemical research2005
Alpha-ketoisocaproic acid increases phosphorylation of intermediate filament proteins from rat cerebral cortex by mechanisms involving Ca2+ and cAMP.
Article in Neurochemical research, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed, 14 citations in OpenAlex.
- Memantine Improves Memory and Neurochemical Damage in a Model of Maple Syrup Urine Disease.Neurochemical research · 2024Article
- Methylphenidate disrupts cytoskeletal homeostasis and reduces membrane-associated lipid content in juvenile rat hippocampus.Metabolic brain disease · 2018Article
- Article
- Cytoskeleton as a potential target in the neuropathology of maple syrup urine disease: insight from animal studies.Journal of inherited metabolic disease · 2007Review
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6 authors at 1 institution in 1 country.
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Abstract
We have previously described that alpha-ketoisocaproic acid (KIC), the main metabolite accumulating in maple syrup urine disease (MSUD), increased the in vitro phosphorylation of cytoskeletal proteins in cerebral cortex of 17- and 21-day-old rats through NMDA glutamatergic receptors. In the present study we investigated the protein kinases involved in the effects of KIC on the phosphorylating system associated with the cytoskeletal fraction and provided an insight on the mechanisms involved in such effects. Results showed that 1 mM KIC increased the in vitro incorporation of 32P into intermediate filament (IF) proteins in slices of 21-day-old rats at shorter incubation times (5 min) than previously reported. Furthermore, this effect was prevented by 10 microM KN-93 and 10 microM H-89, indicating that KIC treatment increased Ca2+/calmodulin- (PKCaMII) and cAMP- (PKA) dependent protein kinases activities, respectively. Nifedipine (100 microM), a blocker of voltage-dependent calcium channels (VDCC), DL-AP5 (100 microM), a NMDA glutamate receptor antagonist and BAPTA-AM (50 microM), a potent intracellular Ca2+ chelator, were also able to prevent KIC-induced increase of in vitro phosphorylation of IF proteins. In addition, KIC treatment was able to significantly increase the intracellular cAMP levels. This data support the view that KIC increased the activity of the second messenger-dependent protein kinases PKCaMII and PKA through intracellular Ca2+ levels. Considering that hyperphosphorylation of cytoskeletal proteins is related to neurodegeneration it is presumed that the Ca2+-dependent hyperphosphorylation of IF proteins caused by KIC may be involved to the neuropathology of MSUD patients.
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