Liraglutide prevents beta-amyloid-induced neurotoxicity in SH-SY5Y cells via a PI3K-dependent signaling pathway.

Abstract:

OBJECTIVES:The aim of the study was to investigate the effects of the GLP-1 analog liraglutide on beta-amyloid (Aβ)-induced neurotoxicity in the human neuroblastoma cell line SH-SY5Y and study the underlying mechanisms. METHODS:Cultured SH-SY5Y cells in vitro were randomly divided into normal control group, beta-amyloid (Aβ) group (20, 40, and 80 uM), and liraglutide pre-treatment group (10, 100, and 200 nM). Cell viability was determined by CCK-8 and lactate dehydrogenase (LDH). Based on its higher protection potentials, the effect of the liraglutide (100 nM) and wortmannin (200 nM) on beta-amyloid (Aβ) group (40 uM) damage in human SH-SY5Ycells was examined by DAPI fluorescence staining and flow cytometry. Caspase-3, Bcl-2, Bax, Cyt-C, Akt, and P-Akt expression were detected by western blotting. RESULTS:We found that exposure of SH-SY5Y to Aβ (25-35)-induced cytotoxicity, increased lactate dehydrogenase (LDH) leakage, and cellular apoptosis. Interestingly, pre-treatment with liraglutide reversed these reactions. Liraglutide afforded protection against Aβ (25-35)-induced toxicity by inhibiting apoptosis, which was also confirmed by the activated caspase-3 assay. P-Akt and Bcl-2/Bax expression increased after pre-treatment with liraglutide in SH-SY5Y cells exposed to Aβ (25-35), whereas cytochrome-c release decreased. This effect could be reversed by wortmannin, an inhibitor of PI3K (phosphoinositide 3-kinase). DISCUSSION:These findings suggest that liraglutide prevented Aβ (25-35)-induced neurotoxicity by inhibiting neuronal apoptosis and liraglutide may have a neuroprotective effect through activation of the PI3K/Akt signaling pathway. Thus, liraglutide may be a preventive or therapeutic agent for Alzheimer's disease.

journal_name

Neurol Res

journal_title

Neurological research

authors

Liu XY,Wang LX,Chen Z,Liu LB

doi

10.1080/01616412.2016.1145914

subject

Has Abstract

pub_date

2016-04-01 00:00:00

pages

313-9

issue

4

eissn

0161-6412

issn

1743-1328

journal_volume

38

pub_type

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