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


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.


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



Advanced glycation endproducts


Reactive oxygen species


AGEs receptor


Nicotinamide adenine dinucleotide phosphate


Alpha-lipoic acid


Endoplasmic reticulum




Superoxide dismutase


Glutathione peroxidase


Glutathione reductase




Apoptosis inducing factor


Unfolded protein response


Glucose-regulated protein 78


Eukaryotic translation initiation factor 2


RAGE-neutralizing antibody


Diphenylene iodonium


Bovine serum aluminum


C/EBP homologous protein


2′,7′-Dichlorofluorescein diacetate


Lactate dehydrogenase


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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