Effect of propionic and methylmalonic acids on the in vitro phosphorylation of intermediate filaments from cerebral cortex of rats during development

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

In this study we investigated the in vivo and in vitro effects of methylmalonic (MMA) and propionic acids (PA), at concentrations usually found in methylmalonic acidemia and propionic acidemia respectively, on the phosphorylation of intermediate filament proteins in cerebral cortex of rats during development. Rats of 9, 12, and 17 days were acutely injected with the acids and sacrificed 90 min after injection. The cerebral cortex was dissected, and slices were incubated with 32P-orthophosphate. The cytoskeletal fraction was extracted and the radioactivity incorporated into intermediate filament subunits was measured. In addition, cortical slices from nontreated rats of 9, 12, 15, 17, 21, and 60 days of life were incubated with the acids in the presence of 32P-orthophosphate, the cytoskeletal fraction was extracted and the radioactivity was measured. Results demonstrated that MMA and PA significantly decreased the radioactivity incorporated into intermediate filament proteins at day 12, both in vivo and in tissue slices. In contrast, PA increased the in vitro phosphorylation of the cytoskeletal proteins in slices of 21-day-old animals. It acts through PP2A and PP2B in 12-day-old rats and through PKA and PKCaMII in 21-day-old animals. We propose that alteration of cytoskeletal protein phosphorylation caused by methylmalonic and propionic acids may be related to the neurological dysfunction characteristic of propionic and methylmalonic acidemia.

Original languageEnglish (US)
Pages (from-to)207-219
Number of pages13
JournalMetabolic Brain Disease
Volume18
Issue number3
DOIs
StatePublished - Sep 2003

Keywords

  • Cerebral cortex
  • Development
  • Intermediate filaments
  • Methylmalonic acid
  • Phosphorylation
  • Propionic acid

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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