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Neuroprotective and anti-apoptotic effects of Liraglutide on SH-SY5Y cells exposed to Methylglyoxal stress

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Neuroprotective and anti-apoptotic effects of Liraglutide on SH-SY5Y cells exposed to Methylglyoxal stress. / Sharma, Mohit; Jalewa, Jaishree; Hölscher, Christian.

In: Journal of Neurochemistry, Vol. 128, No. 3, 02.2014, p. 459-471.

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Sharma, Mohit ; Jalewa, Jaishree ; Hölscher, Christian. / Neuroprotective and anti-apoptotic effects of Liraglutide on SH-SY5Y cells exposed to Methylglyoxal stress. In: Journal of Neurochemistry. 2014 ; Vol. 128, No. 3. pp. 459-471.

Bibtex

@article{cf259c563782476ca45d62aa1197c5fc,
title = "Neuroprotective and anti-apoptotic effects of Liraglutide on SH-SY5Y cells exposed to Methylglyoxal stress",
abstract = "Glucagon-like peptide 1 (GLP-1) is a growth factor that has demonstrated neuroprotective properties in a range of studies. In an APPswe/PS1ΔE9 mouse model of Alzheimer's disease (AD), we previously found protective effects on memory formation, synaptic plasticity, synapse survival and a reduction of amyloid synthesis and plaque load in the brain. Here, we analyse the neuroprotective properties of the GLP-1 analogue liraglutide in human neuroblastoma cell line SH-SY5Y during methyl glyoxal stress. We show for the first time that cell viability was enhanced by liraglutide (XTT assay) in a dose-dependent way, while cytotoxicity (LDH assay) and apoptosis were reduced. Expression of the pro-survival Mcl1 signaling protein was increased, as was activation of cell survival kinases Akt, MEK1/2 and the transcription factor p90RSK. Liraglutide also decreased pro-apoptotic Bax and Bik expression. In addition, the membrane potential and the influx of calcium into the cell were enhanced by liraglutide. GLP-1 receptor expression was also increased by the drug. The results demonstrate a range of growth factor-related cytoprotective processes induced by liraglutide, which is currently on the market as a treatment for type 2 diabetes (Victoza{\textregistered}). It is also tested in clinical trials in patients with Alzheimer disease.",
keywords = "Alzheimer's disease, apoptosis , incretins , insulin , neurodegeneration , neuroprotection",
author = "Mohit Sharma and Jaishree Jalewa and Christian H{\"o}lscher",
note = "{\textcopyright} 2013 International Society for Neurochemistry.",
year = "2014",
month = feb,
doi = "10.1111/jnc.12469",
language = "English",
volume = "128",
pages = "459--471",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "3",

}

RIS

TY - JOUR

T1 - Neuroprotective and anti-apoptotic effects of Liraglutide on SH-SY5Y cells exposed to Methylglyoxal stress

AU - Sharma, Mohit

AU - Jalewa, Jaishree

AU - Hölscher, Christian

N1 - © 2013 International Society for Neurochemistry.

PY - 2014/2

Y1 - 2014/2

N2 - Glucagon-like peptide 1 (GLP-1) is a growth factor that has demonstrated neuroprotective properties in a range of studies. In an APPswe/PS1ΔE9 mouse model of Alzheimer's disease (AD), we previously found protective effects on memory formation, synaptic plasticity, synapse survival and a reduction of amyloid synthesis and plaque load in the brain. Here, we analyse the neuroprotective properties of the GLP-1 analogue liraglutide in human neuroblastoma cell line SH-SY5Y during methyl glyoxal stress. We show for the first time that cell viability was enhanced by liraglutide (XTT assay) in a dose-dependent way, while cytotoxicity (LDH assay) and apoptosis were reduced. Expression of the pro-survival Mcl1 signaling protein was increased, as was activation of cell survival kinases Akt, MEK1/2 and the transcription factor p90RSK. Liraglutide also decreased pro-apoptotic Bax and Bik expression. In addition, the membrane potential and the influx of calcium into the cell were enhanced by liraglutide. GLP-1 receptor expression was also increased by the drug. The results demonstrate a range of growth factor-related cytoprotective processes induced by liraglutide, which is currently on the market as a treatment for type 2 diabetes (Victoza®). It is also tested in clinical trials in patients with Alzheimer disease.

AB - Glucagon-like peptide 1 (GLP-1) is a growth factor that has demonstrated neuroprotective properties in a range of studies. In an APPswe/PS1ΔE9 mouse model of Alzheimer's disease (AD), we previously found protective effects on memory formation, synaptic plasticity, synapse survival and a reduction of amyloid synthesis and plaque load in the brain. Here, we analyse the neuroprotective properties of the GLP-1 analogue liraglutide in human neuroblastoma cell line SH-SY5Y during methyl glyoxal stress. We show for the first time that cell viability was enhanced by liraglutide (XTT assay) in a dose-dependent way, while cytotoxicity (LDH assay) and apoptosis were reduced. Expression of the pro-survival Mcl1 signaling protein was increased, as was activation of cell survival kinases Akt, MEK1/2 and the transcription factor p90RSK. Liraglutide also decreased pro-apoptotic Bax and Bik expression. In addition, the membrane potential and the influx of calcium into the cell were enhanced by liraglutide. GLP-1 receptor expression was also increased by the drug. The results demonstrate a range of growth factor-related cytoprotective processes induced by liraglutide, which is currently on the market as a treatment for type 2 diabetes (Victoza®). It is also tested in clinical trials in patients with Alzheimer disease.

KW - Alzheimer's disease

KW - apoptosis

KW - incretins

KW - insulin

KW - neurodegeneration

KW - neuroprotection

U2 - 10.1111/jnc.12469

DO - 10.1111/jnc.12469

M3 - Journal article

C2 - 24112036

VL - 128

SP - 459

EP - 471

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 3

ER -