Okadaic acid–induced tau hyperphosphorylation and the downregulation of Pin1 expression in primary cortical neurons

Derya Metin-Armağan, Duygu Gezen-Ak, Erdinç Dursun, İrem Lütfiye Atasoy, Arzu Karabay, Selma Yılmazer, Melek Öztürk*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

Abstract

Hyperphosphorylation of tau leading to neurofibrillary tangles (NFT) is one of the key pathological hallmarks in neurodegenerative disorders such as Alzheimer disease (AD). Peptidyl-prolyl cis-trans isomerase (Pin1) regulates the phosphorylation of Ser/Thr sites of tau protein, and promotes microtubule assembly. In this study, we aimed to determine the effect of tau hyperphosphorylation on Pin1 expression in primary cortical neurons in order to investigate the results of the pathological process on Pin1, an important enzyme involved in various cellular mechanisms. Primary cortical neurons were prepared from embryonic day 16 -Sprague Dawley rat embryos. The cultures were treated with 25 nM okadaic acid (OKA) on day 7 in order to promote tau hyperphosphorylation. The cytotoxicity was determined with LDH release and measured by ELISA. Tau phosphorylation was confirmed by western blot using anti-tau antibodies Thr231 and Tau-1. Pin1 mRNA expression level was determined by qRT-PCR at 8 and 24 h. Pin1 protein expression was analyzed with immunofluorescent labeling at 8 and 24 h. Tau phosphorylation on Thr231 was increased and non-phosphorylated Tau-1 was decreased in OKA treated group compared with the untreated control at 8 h of treatment. While Pin1 mRNA expression levels at 8 h post-OKA treatment were lower than that of control groups, there were no differences between OKA-treated group and control groups in Pin1 protein expression. Whereas no significant differences for Pin1 mRNA expression, protein expression levels were decreased OKA-treated group compared to control groups at 24 h of treatment. The LDH release of OKA-treated group was significantly increased at 24 h. Our study indicates that although OKA treatment suppressed Pin1 mRNA expression and induced tau phosphorylation at 8 h of treatment, its influence on Pin1 protein expression has 16 h phase delay. Given the important role of Pin1 in many cellular mechanisms these results might indicate that tau hyperphosphorylation involved in many neurodegenerative disorders may cause some alterations in brain microenvironment via Pin1.This is the first demonstration of the alteration of the Pin1 mRNA and protein expression in OKA induced model in primary cortical neurons.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalJournal of Chemical Neuroanatomy
Volume92
DOIs
Publication statusPublished - Oct 2018

Bibliographical note

Publisher Copyright:
© 2018 Elsevier B.V.

Funding

The present study was supported by the Research Fund of Istanbul University (Project No: 21342 and 22455).

FundersFunder number
Istanbul Üniversitesi21342, 22455

    Keywords

    • Alzheimer's disease
    • OKA
    • Pin1
    • Primary cortical neuron
    • Tau
    • Tauopathy

    Fingerprint

    Dive into the research topics of 'Okadaic acid–induced tau hyperphosphorylation and the downregulation of Pin1 expression in primary cortical neurons'. Together they form a unique fingerprint.

    Cite this