Cytotoxic role of advanced glycation end-products in PC12 cells treated with β-amyloid peptide

Abstract

Alzheimer's disease (AD) is the most common type of dementia afflicting the elderly. Recent studies have increasingly suggested that a high concentration of advanced glycation end products (AGEs) may be important in AD pathogenesis. However, the mechanisms and pathways involved remain unknown. The aim of this study was to explore whether the mechanism of the effect of AGEs on Aβ‑PC12 cells [PC12 cells treated with β‑amyloid (Aβ) peptide] was associated with oxidative stress; and to study whether inhibiting the activity of the receptor for AGE (RAGE) attenuated the toxic effect of AGEs and Aβ on PC12 cells. Several PC12 cells were pretreated with Aβ, and were then treated with different concentrations of AGEs. Other PC12 cells were treated with trypsin, a pancreatic protein enzyme and an inhibitor of RAGE, and were then treated with Aβ and AGEs. Apoptosis was measured by flow cytometry (FCM) and cell viability was measured by MTT assay. RAGE and nuclear factor‑κB (NF‑κB) were measured by reverse transcription-polymerase chain reaction (RT‑PCR) assay. With an increase in AGE concentration, the viability of Aβ‑PC12 cells treated with AGEs decreased. However, the Aβ‑PC12 cell viability was greater in the trypsin group than in the non‑trypsin group. Cell apoptosis rates and mRNA expression of RAGE and NF‑κB in Aβ‑PC12 cells treated with AGEs were significantly higher than in the Aβ‑PC12 cells. AGEs and Aβ were neurotoxic, and RAGE triggered the neural cytotoxic role of AGEs in Aβ‑PC12 cells. The molecular mechanisms may be connected with the expression of NF‑κB and apoptosis mediated by RAGE. Inhibiting the activity of RAGE may mitigate the toxic effect of AGEs and Aβ on neural cells.