Okadaic acid induces early changes in microtubule-associated protein 2 and τ phosphorylation prior to neurodegeneration in cultured cortical neurons

Clorinda Arias, Nishi Sharma, Peter Davies, Bridget Shafit-Zagardo

Research output: Contribution to journalArticle

118 Citations (Scopus)

Abstract

Microtubules and their associated proteins play a prominent role in many physiological and morphological aspects of brain function. Abnormal deposition of the microtubule-associated proteins (MAPs), MAP2 and τ, is a prominent aspect of Alzheimer's disease. MAP2 and τ are heat-stable phosphoproteins subject to high rates of phosphorylation/dephosphorylation. The phosphorylation state of these proteins modulates their affinity for tubulin and thereby affects the structure of the neuronal cytoskeleton. The dinoflagellate toxin okadaic acid is a potent and specific inhibitor of protein phosphatases 1 and 2A. In cultured rat cortical neurons and a human neuroblastoma cell line (MSN), okadaic acid induces increased phosphorylation of MAP2 and τ concomitant with early changes in the neuronal cytoskeleton and ultimately leads to cell death. These results suggest that the diminished rate of MAP2 and τ dephosphorylation affects the stability of the neuronal cytoskeleton. The effect of okadaic acid was not restricted to neurons. Astrocytes stained with antibodies to glial fibrillary acidic protein (GFAP) showed increased GFAP staining and changes in astrocyte morphology from a flat shape to a stellate appearance with long processes.

Original languageEnglish (US)
Pages (from-to)673-682
Number of pages10
JournalJournal of Neurochemistry
Volume61
Issue number2
StatePublished - Aug 1993

Fingerprint

Okadaic Acid
Phosphorylation
Microtubule-Associated Proteins
Cytoskeleton
Neurons
Glial Fibrillary Acidic Protein
Astrocytes
Dinoflagellida
Protein Phosphatase 2
Phosphoproteins
Cell death
Tubulin
Neuroblastoma
Rats
Brain
Alzheimer Disease
Cell Death
Hot Temperature
Cells
Staining and Labeling

Keywords

  • Cytoskeleton
  • Microtubule-associated proteins
  • Neurotoxicity
  • Okadaic acid
  • Phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Okadaic acid induces early changes in microtubule-associated protein 2 and τ phosphorylation prior to neurodegeneration in cultured cortical neurons. / Arias, Clorinda; Sharma, Nishi; Davies, Peter; Shafit-Zagardo, Bridget.

In: Journal of Neurochemistry, Vol. 61, No. 2, 08.1993, p. 673-682.

Research output: Contribution to journalArticle

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