Cellular and Molecular Neurobiology

, Volume 32, Issue 8, pp 1299–1309

AGEs Induce Cell Death via Oxidative and Endoplasmic Reticulum Stresses in Both Human SH-SY5Y Neuroblastoma Cells and Rat Cortical Neurons

  • Qing-Qing Yin
  • Chuan-Fang Dong
  • Si-Qin Dong
  • Xue-Li Dong
  • Yan Hong
  • Xun-Yao Hou
  • Ding-Zhen Luo
  • Jin-Jing Pei
  • Xue-Ping Liu
Original Paper

Abstract

Advanced glycation endproducts (AGEs) are elevated in aging and neurodegenerative diseases such as Alzheimer’s disease (AD), and they can stimulate the generation of reactive oxygen species (ROSs) via NADPH oxidase, induce oxidative stress that lead to cell death. In the current study, we investigated the molecular events underlying the process that AGEs induce cell death in SH-SY5Y cells and rat cortical neurons. We found: (1) AGEs increase intracellular ROSs; (2) AGEs cause cell death after ROSs increase; (3) oxidative stress-induced cell death is inhibited via the blockage of AGEs receptor (RAGE), the down-regulation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and the increase of scavenging by anti-oxidant alpha-lipoic acid (ALA); (4) endoplasmic reticulum (ER) stress was triggered by AGE-induced oxidative stress, resulting in the activation of C/EBP homologous protein (CHOP) and caspase-12 that consequently initiates cell death, taurine-conjugated ursodeoxycholic acid (TUDCA) inhibited AGE-induced ER stress and cell death. Blocking RAGE–NADPH oxidase, and RAGE–NADPH oxidase–ROSs and ER stress scavenging pathways could efficiently prevent the oxidative and ER stresses, and consequently inhibited cell death. Our results suggest a new prevention and or therapeutic approach in AGE-induced cell death.

Keywords

Advanced glycation endproducts Reactive oxygen species NADPH oxidase Oxidative stress Endoplasmic reticulum stress Apoptosis 

Abbreviations

AGEs

Advanced glycation endproducts

ROSs

Reactive oxygen species

RAGE

AGEs receptor

NADPH

Nicotinamide adenine dinucleotide phosphate

ALA

Alpha-lipoic acid

ER

Endoplasmic reticulum

MDA

Malondialdehyde

SOD

Superoxide dismutase

GSH-Px

Glutathione peroxidase

GR

Glutathione reductase

CAT

Catalase

AIF

Apoptosis inducing factor

UPR

Unfolded protein response

GRP78

Glucose-regulated protein 78

eIF2α

Eukaryotic translation initiation factor 2

RAGE-ab

RAGE-neutralizing antibody

DPI

Diphenylene iodonium

BSA

Bovine serum aluminum

CHOP

C/EBP homologous protein

DCFH-DA

2′,7′-Dichlorofluorescein diacetate

LDH

Lactate dehydrogenase

PERK

Double-stranded RNA-activated protein kinase-like ER kinase

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Qing-Qing Yin
    • 1
  • Chuan-Fang Dong
    • 1
  • Si-Qin Dong
    • 1
  • Xue-Li Dong
    • 2
  • Yan Hong
    • 1
  • Xun-Yao Hou
    • 1
  • Ding-Zhen Luo
    • 1
  • Jin-Jing Pei
    • 3
  • Xue-Ping Liu
    • 1
    • 2
  1. 1.Department of Senile NeurologyProvincial Hospital Affiliated to Shandong UniversityJinanChina
  2. 2.Department of Anti-AgeingProvincial Hospital Affiliated to Shandong UniversityJinanChina
  3. 3.Department of KI-Alzheimer Disease Research CenterKarolinska InstitutetStockholmSweden

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