Apolipoprotein E (ApoE) peptide regulates tau phosphorylation via two different signaling pathways
| Autor: | Eric Gruenstein, Xiao-shu Wang, Patricia Luebbe, Frank P. Zemlan |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Apolipoprotein E
Cytoplasm Antifungal Agents Time Factors Molecular Sequence Data Tau protein Phosphatase Enzyme-Linked Immunosorbent Assay tau Proteins Rats Sprague-Dawley Dephosphorylation Cellular and Molecular Neuroscience chemistry.chemical_compound Apolipoproteins E Cyclosporin a Okadaic Acid Animals Spiro Compounds Amino Acid Sequence Virulence Factors Bordetella Enzyme Inhibitors Phosphorylation Pyrans Neurons Dose-Response Relationship Drug biology Chemistry Antibodies Monoclonal Okadaic acid Molecular biology Peptide Fragments Phosphoric Monoester Hydrolases Rats Cyclosporine biology.protein Calcium Signal transduction Immunosuppressive Agents Signal Transduction |
| Zdroj: | Journal of Neuroscience Research. 51:658-665 |
| ISSN: | 1097-4547 0360-4012 |
| DOI: | 10.1002/(sici)1097-4547(19980301)51:5<658::aid-jnr13>3.0.co;2-z |
| Popis: | Previous studies have shown that treating rat cortical neurons in primary culture with apolipoprotein E (apoE) peptide increased cytoplasmic Ca2+ by 2 mechanisms: 1) an influx of extracellular Ca2+ resulting from the activation of a cell surface Ca2+ channel; and 2) release of Ca2+ from internal Ca2+ stores via a G-protein-coupled pathway (Wang and Gruenstein, 1997). These studies employed a biologically active apoE synthetic peptide (apoEdp) derived from the receptor binding domain of apoE. In the present study we examined whether activation of these 2 signal transduction pathways affects phosphorylation of microtubule-associated protein tau. The levels of tau phosphorylation at thr231, ser235, and ser396 were quantified by ELISA employing monoclonal antibodies PHF-6, SMI33, and PHF-1. ApoEdp treatment resulted in a concentration- and time-dependent dephosphorylation of tau at all 3 phosphorylation sites. The apoEdp-induced dephosphorylation of tau at thr231, and ser235 was dependent on the influx of extracellular Ca2+, while dephosphorylation at ser396 was mediated by a pertusis toxin-sensitive G-protein pathway. The involvement of protein phosphatases in mediating the apoEdp-induced dephosphorylation of tau was examined. Pretreatment with the protein phosphatase 2B inhibitor cyclosporin A blocked the apoEdp-induced dephosphorylation of tau at thr231 and ser235 but not at ser396. Pretreatment with the protein phosophatase 2A/1 inhibitor okadaic acid blocked the apoEdp-induced dephosphorylation of tau at all 3 sites, while pretreatment with the protein phosphates 1 inhibitor tautomycin was without effect. The present study suggests that apoE may affect several Ca2+-associated signal transduction pathways that increase the activity of protein phosphatases 2A and 2B, which in turn dephosphorylate tau. J. Neurosci. Res. 51:658–665, 1998. © 1998 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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