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- Title
Attenuation of okadaic acid-induced hyperphosphorylation of cytoskeletal proteins by heat preconditioning and its possible underlying mechanisms.
- Authors
Ya Fei Xu; Yong Jie Zhang; Ai Hong Zhang; Qi Zhang; Tangchun Wu; Jian-Zhi Wang
- Abstract
An imbalanced phosphorylation system is recognized to be one of the main reasons for Alzheimer-like hyperphosphorylation of cytoskeletal proteins. However, little is known about the strategies rectifying the lesions caused by this disrupted phosphorylation. To search for the means to arrest Alzheimer-like damages and explore the underlying mechanisms, in this study we treated N2a/peuht40 cells with okadaic acid (OA), a specific inhibitor of protein phosphatase-2A (PP-2A) and PP-1, to mimic an Alzheimer-like phosphatase-deficient system and then used heat preconditioning (42°C for 1 hour) to induce the expression of inducible heat shock protein 70 (Hsp70) in the cells. We observed that heat preconditioning arrested OA-induced hyperphosphorylation of neurofilament (NF) protein at SMI34 and SMI33 epitopes as well as hyperphosphorylation of tau at Tau-1 and PHF-1 epitopes. It counteracted OA-induced decrease in PP-2A activity with a concurrent inhibition in constitutive activity of mitogen-activated protein kinases (MAPKs) and cyclic adenosine 5'-monophosphate-dependent protein kinase A (PKA). Conversely, quercetin, a recognized blocker of stress-responsive Hsp70 expression, diminished the effects caused by heat preconditioning. These results suggested that Hsp70 antagonized OA-induced Alzheimer-like NF and tau hyperphosphorylation, and the restoration of PP-2A and inhibition of MAPKS-PKA activity might be part of the underlying mechanisms for the rectification of OA-induced hyperphosphorylation.
- Publication
Cell Stress & Chaperones, 2004, Vol 9, Issue 3, p304
- ISSN
1355-8145
- Publication type
Academic Journal
- DOI
10.1379/CSC-23R1.1