Advanced glycation end products induce oxidative stress and mitochondrial dysfunction in SH-SY5Y cells.
This study aimed to investigate the direct effects of advanced glycation end products (AGEs) on the mitochondrial structure and function of SH-SY5Y cells and the possible molecular mechanism(s) underlying mitochondria dysfunction by AGEs. SH-SY5Y cells were cultured in 400 μg/ml of AGE-bovine serum albumin (BSA) for 24 h, and changes in the mitochondrial function of SH-SY5Y cells were analysed as follows. Reactive oxygen species (ROS) were detected using 2',7'-dichlorodihydrofluorescein diacetate molecular probes. Mitochondrial membrane potential (ΔΨm) was determined by flow cytometry using fluorescent probes. The expression of cytochrome c (Cyt c) protein level was assessed by Western blotting. Mitochondrial structures were observed by transmission electron microscopy. Our results showed that AGE-BSA induced an increase in ROS levels, a decrease in mitochondrial ΔΨm, and the release of Cyt c from mitochondria in SH-SY5Y cells. The mitochondria of SH-SY5Y cells showed remarkable swelling and vacuolisation, but these changes were recovered after pretreatment with neutralising anti-receptor for advanced glycation end products (RAGE) antibody. Our results suggested that AGE-BSA induced mitochondrial dysfunction in SH-SY5Y cells through RAGE pathways. Thus, AGEs are potential mechanistic links between diabetes mellitus and Alzheimer's disease.
Basic Medicine Combined with Chinese Traditional Medicine and Western Medicine, Liaoning University of Traditional Chinese Medicine, Shenyang, 110847, People's Republic of China, wangxu19790412@hotmail.com.
Xu
X
Wang
Song
S
Yu
Chun-Yan
CY
Wang
Yue
Y
Wang
Hai-Xing
HX
Liu
Yong
Y
Cui
Li-De
LD
Zhang
D045744:Cell Line, Tumor / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009447:Neuroblastoma / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D000067759:Receptor for Advanced Glycation End Products / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology
D017127:Glycation End Products, Advanced; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; C081628:advanced glycation end products-bovine serum albumin; D012710:Serum Albumin, Bovine; D045304:Cytochromes c