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Metabolic Brain Disease

, Volume 21, Issue 1, pp 49–60 | Cite as

Propionic Acid Induces Cytoskeletal Alterations in Cultured Astrocytes From Rat Cerebral Cortex

  • Lúcia Maria Vieira de Almeida
  • Cláudia Funchal
  • Carmem Gottfried
  • Moacir Wajner
  • Regina Pessoa-PureurEmail author
Original Paper

Abstract

Severe neurological symptoms, cerebral edema, and atrophy are common features of the inherited metabolic disorder propionic acidemia. However, the pathomechanisms involved in the neuropathology of this disease are not well established. In this study, we investigate the effects of propionic acid (PA), a metabolite accumulating in this disorder, on cytoskeletal reorganization, on cell viability, and on the in vitro phosphorylation of glial fibrillary acidic protein (GFAP) and vimentin in cultured astrocytes from cerebral cortex of neonatal rats. We observed that the astrocytes changed their usual polygonal morphology when exposed to 5 mM PA for 72 h, leading to the appearance of fusiform or process-bearing cells, without elicit cell death. We also noticed that after 72 h treatment with 5 mM PA cells showed retracted cytoplasm with bipolar processes containing packed GFAP filaments and disorganized actin stress fibers, as revealed by immunocytochemistry. In addition, the morphological alterations were accompanied by increased in vitro 32P incorporation into GFAP and vimentin recovered into the high-salt Triton-insoluble cytoskeletal fraction. In conclusion, our results indicate that PA lead to cytoskeletal reorganization and to increased in vitro phosphorylation of Triton-insoluble GFAP and vimentin. On the basis of our results we could suppose that Triton-insoluble GFAP and vimentin hyperphosphorylation could be implicated in the reorganization of cellular structure and these findings could be involved in the brain damage characteristic of propionic acidemia patients.

Keywords

Propionic acid Cytoskeleton Actin GFAP Vimentin Phosphorylation 

Notes

Acknowledgments

This work was supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), PRONEX and Pró-Reitoria de Pesquisa e Pós-Graduação da Universidade Federal do Rio Grande do Sul (PROPESq-UFRGS).

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Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Lúcia Maria Vieira de Almeida
    • 1
  • Cláudia Funchal
    • 1
  • Carmem Gottfried
    • 1
  • Moacir Wajner
    • 1
  • Regina Pessoa-Pureur
    • 1
    Email author
  1. 1.Departamento de BioquímicaInstituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do SulRua Ramiro Barcelos 2600 anexoBrasil

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