Calreticulin Binds to Fas Ligand and Inhibits Neuronal Cell Apoptosis Induced by Ischemia-Reperfusion Injury

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2015 Nov 20

PMID 26583143

Citations 11

Authors

Beilei Chen

Zhengzheng Wu

Jun Xu

Yun Xu

Affiliations

Soon will be listed here.

Abstract

Background: Calreticulin (CRT) can bind to Fas ligand (FasL) and inhibit Fas/FasL-mediated apoptosis of Jurkat T cells. However, its effect on neuronal cell apoptosis has not been investigated.

Purpose: We aimed to evaluate the neuroprotective effect of CRT following ischemia-reperfusion injury (IRI).

Methods: Mice underwent middle cerebral artery occlusion (MCAO) and SH-SY5Y cells subjected to oxygen glucose deprivation (OGD) were used as models for IRI. The CRT protein level was detected by Western blotting, and mRNA expression of CRT, caspase-3, and caspase-8 was measured by real-time PCR. Immunofluorescence was used to assess the localization of CRT and FasL. The interaction of CRT with FasL was verified by coimmunoprecipitation. SH-SY5Y cell viability was determined by MTT assay, and cell apoptosis was assessed by flow cytometry. The measurement of caspase-8 and caspase-3 activity was carried out using caspase activity assay kits.

Results: After IRI, CRT was upregulated on the neuron surface and bound to FasL, leading to increased viability of OGD-exposed SH-SY5Y cells and decreased activity of caspase-8 and caspase-3.

Conclusions: This study for the first time revealed that increased CRT inhibited Fas/FasL-mediated neuronal cell apoptosis during the early stage of ischemic stroke, suggesting it to be a potential protector activated soon after IRI.

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