Advanced glycation end products induce oxidative stress and mitochondrial dysfunction in SH-SY5Y cells

• Published in: In vitro cellular & developmental biology. Animal Vol. 51; no. 2; pp. 204 - 209
• Main Authors: Wang, Xu, Yu, Song, Wang, Chun-Yan, Wang, Yue, Liu, Hai-Xing, Cui, Yong, Zhang, Li-De
• Format: Journal Article
• Language: English
• Published: Boston Springer-Verlag 01.02.2015; Springer Science & Business Media LLC; Springer US; Society for In Vitro Biology
• Subjects: advanced glycation end products; Alzheimer disease; Animal Genetics and Genomics; Biomedical and Life Sciences; Cell Biology; Cell Culture; Cell Line, Tumor - drug effects; CELLULAR PATHOLOGY/VIROLOGY; cultured cells; cytochrome c; Cytochromes c - metabolism; Developmental Biology; diabetes mellitus; flow cytometry; fluorescence; Glycation End Products, Advanced - pharmacology; Humans; Life Sciences; membrane potential; Membrane Potential, Mitochondrial - drug effects; mitochondria; Mitochondria - drug effects; Mitochondria - metabolism; mitochondrial membrane; Neuroblastoma - pathology; neutralization; oxidative stress; Oxidative Stress - drug effects; reactive oxygen species; Reactive Oxygen Species - metabolism; Receptor for Advanced Glycation End Products - metabolism; serum albumin; Serum Albumin, Bovine - pharmacology; Stem Cells; transmission electron microscopy; Western blotting; SH-SY5Y; Oxidative stress; Mitochondria; AGEs
• ISSN: 1071-2690; 1543-706X
• DOI: 10.1007/s11626-014-9823-5

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.