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Production of paired helical filament, tau‐like proteins by PC12 cells: A model of neurofibrillary degeneration
Author(s) -
Bondareff William,
Matsuyama Steven S.,
Dell'Albani Paola
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19980601)52:5<498::aid-jnr2>3.0.co;2-7
Subject(s) - microtubule , cytoplasm , microbiology and biotechnology , tau protein , epitope , mitochondrion , chemistry , heat shock protein , intracellular , electron microscope , colcemid , cytoskeleton , biophysics , tubulin , biology , pathology , cell , biochemistry , antibody , alzheimer's disease , immunology , medicine , physics , disease , gene , optics
Neuron‐like cells derived from a rat pheochromocytoma cell line (PC12) and differentiated with nerve growth factor produce a paired helical filament (PHF)‐like antigen when they are subjected to heat shock (Wallace et al.: Mol Brain Res 19:149–155, 1993). It accumulates in a localized region of the perinuclear cytoplasm and reacts with monoclonal antitau antibodies, which identify epitopes in the N‐ and C‐terminal halves and the microtubule‐binding domain of tau protein. The observed profile of immunoreactivity suggests the presence of full‐length and C‐terminally truncated tau in a region of perinuclear cytoplasm in which no structurally intact PHFs could be demonstrated by conventional transmission electron microscopy. The accumulated tau protein colocalized with antibodies raised against mitochondrial outer membrane proteins and was associated with the presence of numerous mitochondrial profiles that were demonstrated with electron microscopy. Because differentiated PC12 cells pretreated with colcemid or Taxol prior to heat shock fail to exhibit perinuclear PHF‐like immunoreactivity, the reported response to heat shock appears to require an intact system of intracellular microtubules. This PC12 system provides a model in which the metabolic and molecular biological underpinnings of neuronal degeneration in Alzheimer's disease can be manipulated. The system may eventually be applicable to the development of pharmaceutical agents that interfere with formation and/or degeneration of PHF‐tau in Alzheimer's disease. J. Neurosci. Res. 52:498–504, 1998. © 1998 Wiley‐Liss, Inc.