Department of Neurology, Zhongda Hospital of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Mol Med Rep. 2013 Aug;8(2):367-72. doi: 10.3892/mmr.2013.1545. Epub 2013 Jun 25.
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.
阿尔茨海默病（AD）是最常见的老年痴呆症类型。最近的研究越来越表明，高水平的晚期糖基化终产物（AGEs）可能在 AD 的发病机制中起重要作用。然而，涉及的机制和途径仍不清楚。本研究旨在探讨 AGEs 对 Aβ-PC12 细胞（用β-淀粉样蛋白（Aβ）肽处理的 PC12 细胞）的影响机制是否与氧化应激有关；并研究抑制 AGE 受体（RAGE）的活性是否能减弱 AGEs 和 Aβ 对 PC12 细胞的毒性作用。一些 PC12 细胞先用 Aβ 预处理，然后用不同浓度的 AGEs 处理。其他 PC12 细胞先用胰蛋白酶（一种胰腺蛋白酶和 RAGE 的抑制剂）处理，然后用 Aβ 和 AGEs 处理。用流式细胞术（FCM）测量细胞凋亡，用 MTT 测定法测量细胞活力。用逆转录-聚合酶链反应（RT-PCR）法测量 RAGE 和核因子-κB（NF-κB）。随着 AGE 浓度的增加，用 AGEs 处理的 Aβ-PC12 细胞的活力降低。然而，在胰蛋白酶组中 Aβ-PC12 细胞的活力大于非胰蛋白酶组。用 AGEs 处理的 Aβ-PC12 细胞的细胞凋亡率和 RAGE 和 NF-κB 的 mRNA 表达明显高于 Aβ-PC12 细胞。AGEs 和 Aβ 具有神经毒性，RAGE 触发了 AGEs 在 Aβ-PC12 细胞中的神经细胞毒性作用。其分子机制可能与 RAGE 介导的 NF-κB 表达和细胞凋亡有关。抑制 RAGE 的活性可能减轻 AGEs 和 Aβ 对神经细胞的毒性作用。
