Okadaic acid induces hyperphosphorylated forms of tau protein in human brain slices.
Publication/Presentation Date
1-1-1993
Abstract
Hyperphosphorylated forms of the microtubule-associated protein tau are components of the paired helical filaments (PHFs) seen in patients with Alzheimer's disease. Slices of human lateral temporal cortex were obtained from tissues removed incidental to resections for intractable hippocampal epilepsy. Tau phosphorylation in temporal lobe slices was determined using mobility shifts after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunodetection with the monoclonal antibodies Alz-50, 5E2, and Tau-1. The results indicate that tau phosphorylation was altered in a dose-dependent manner by the phosphatase inhibitor okadaic acid, but not by N-methyl-D-aspartate, quisqualate, or kainate. The slowest mobility forms of tau, termed "PHF-like tau," produced by okadaic acid treatment were dephosphorylated by purified protein phosphatase 2B (calcineurin). Formation of PHF-like tau peptides was blocked by KN-62, 1[N,O-bis(1,5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazi ne, an inhibitor of Ca2+/calmodulin-dependent protein kinase II. The protein kinase inhibitor staurosporine also prevented formation of PHF-like tau. These data suggest that phosphorylation of tau is regulated by Ca(2+)-dependent protein kinases and okadaic acid-sensitive protein phosphatases, alterations of which may be implicated in the pathogenesis of Alzheimer's disease.
Volume
33
Issue
1
First Page
77
Last Page
87
ISSN
0364-5134
Published In/Presented At
Harris, K. A., Oyler, G. A., Doolittle, G. M., Vincent, I., Lehman, R. A., Kincaid, R. L., & Billingsley, M. L. (1993). Okadaic acid induces hyperphosphorylated forms of tau protein in human brain slices. Annals of neurology, 33(1), 77–87. https://doi.org/10.1002/ana.410330113
Disciplines
Medicine and Health Sciences
PubMedID
8494335
Department(s)
Department of Medicine
Document Type
Article