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Okadaic Acid Induces Early Changes in Microtubule‐Associated Protein 2 and γ Phosphorylation Prior to Neurodegeneration in Cultured Cortical Neurons
Author(s) -
Arias Clorinda,
Sharma Nishi,
Davies Peter,
ShafitZagardo Bridget
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb02172.x
Subject(s) - okadaic acid , dephosphorylation , neurodegeneration , biology , microbiology and biotechnology , phosphorylation , microtubule associated protein , cytoskeleton , tau protein , glial fibrillary acidic protein , astrocyte , phosphatase , microtubule , biochemistry , neuroscience , alzheimer's disease , cell , medicine , central nervous system , immunohistochemistry , disease , immunology
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 γ , is a prominent aspect of Alzheimer's disease. MAP2 and γ 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 γ concomitant with early changes in the neuronal cytoskeleton and ultimately leads to cell death. These results suggest that the diminished rate of MAP2 and γ 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.