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

Abstract

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.

Does Protein Glycation Impact on the Drought-Related Changes in Metabolism and Nutritional Properties of Mature Pea (Pisum sativum L.) Seeds?

“…The primary target of AGEs at the membrane of mammalian cells is the receptor to advanced glycation end products (RAGE) [59], interaction with which is currently recognized as the main mechanism underlying AGE-induced inflammatory response [60]. The human SH-SY5Y cells also express this receptor, and often used to probe pro-and anti-inflammatory effects, also in the context of the Maillard reaction products [61][62][63]. Therefore, here we used this cell line to characterize prospective pro-inflammatory effects of AGEs, bound to the proteins, isolated from the seeds of drought-treated pea plants.…”

Drought-related Changes in the Metabolism and Nutritional Properties of Mature Pea (<em>Pisum sativum L.</em>) Seeds in the Context of Protein Glycation

“…The primary target of AGEs at the membrane of mammalian cells is the receptor to advanced glycation end products (RAGE) [61], interaction with which is currently recognized as the main mechanism underlying AGE-induced inflammatory response [62]. The human SH-SY5Y cells also express this receptor, and often used to probe pro-and anti-inflammatory effects, also in the context of the Maillard reaction products [63][64][65]. Therefore here we used this cell line to characterize prospective pro-inflammatory effects of AGEs, bound to the proteins, isolated from the seeds of drought-treated pea plants.…”

A Bibenzyl Component Moscatilin Mitigates Glycation-Mediated Damages in an SH-SY5Y Cell Model of Neurodegenerative Diseases through AMPK Activation and RAGE/NF-κB Pathway Suppression

“…The SH-SY5Y-derived neurons have become a popular cell model for investigating neurodegenerative diseases [ 22 ]. SH-SY5Y cells have also been utilized in neuropathy models, showing the effects of high glucose and AGEs [ 23 ]. In the present study, AGEs-induced injury in SH-SY5Y neuronal cells was used as an in vitro diabetic/hyperglycemia-associated neurodegenerative disease.…”