AGEs Induce Cell Death via Oxidative and Endoplasmic Reticulum Stresses in Both Human SH-SY5Y Neuroblastoma Cells and Rat Cortical Neurons
作者
Yin, QQ;Dong, CF;Dong, SQ;Dong, XL;Hong, Y;Hou, XY;Luo, DZ;Pei, JJ;Liu, XP
作者单位
[Yin, Qing-Qing; Dong, Chuan-Fang; Dong, Si-Qin; Hong, Yan; Hou, Xun-Yao; Luo, Ding-Zhen; Liu, Xue-Ping] Shandong Univ, Dept Senile Neurol, Prov Hosp, Jinan 250021, Shandong, Peoples R China.;-;[Dong, Xue-Li; Liu, Xue-Ping] Shandong Univ, Dept Antiageing, Prov Hosp, Jinan 250021, Shandong, Peoples R China.;-;[Pei, Jin-Jing] Karolinska Inst, Dept KI, Alzheimer Dis Res Ctr, S-14186 Stockholm, Sweden.
摘要
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.
关键词
GLYCATION END-PRODUCTS; UNFOLDED PROTEIN RESPONSE; REACTIVE OXYGEN; ER STRESS; NEURODEGENERATIVE DISEASES; DIABETIC-NEPHROPATHY; ALZHEIMERS-DISEASE; GENE-EXPRESSION; NADPH OXIDASE; AMYLOID-BETA
基本信息
