当前位置： SCI文献检索 > JOURNAL OF NEUROSCIENCE RESEARCH期刊下所有文献 > Apolipoprotein E (ApoE) peptide regulates tau phosphorylation via two different signaling pathways.

Apolipoprotein E (ApoE) peptide regulates tau phosphorylation via two different signaling pathways.

Abstract：

: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.

journal_name

J Neurosci Res

journal_title

Journal of neuroscience research

authors

Wang X,Luebbe P,Gruenstein E,Zemlan F

doi

10.1002/(SICI)1097-4547(19980301)51:5<658::AID-JNR

subject

Has Abstract

pub_date

1998-03-01 00:00:00

pages

658-65

issue

eissn

0360-4012

issn

1097-4547

pii

10.1002/(SICI)1097-4547(19980301)51:5<658::AID-JNR

journal_volume

pub_type

杂志文章

在线工具

Apolipoprotein E (ApoE) peptide regulates tau phosphorylation via two different signaling pathways.