Neurotoxicity of advanced glycation end-products for cultured cortical neurons
Neurotoxicity of advanced glycation end-products for cultured cortical neurons
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DOI：
10.1093/jnen/59.12.1094
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发表时间：
2000-12-01
影响因子：
3.2
通讯作者：
Makita, Z
中科院分区：
文献类型：
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作者：
Takeuchi, M;Bucala, R;Makita, Z
导致晚期糖基化终产物（AGEs）形成的美拉德反应在糖尿病患者血管病变和衰老的发病机制中起着重要作用。AGEs也被认为有助于阿尔茨海默病（AD）和其他神经退行性过程的病理。用5种免疫化学上不同的AGEs （AGEs-1至-5）孵育皮质神经元，通过MTT试验、台斑蓝和Hoechst 33258染色评估，神经元细胞死亡呈剂量依赖性增加。研究发现，指定为AGE-2的结构表位具有最大的细胞病变作用，并且AGE-2的神经毒性可以通过添加抗AGE-2特异性抗体而不是其他类型的抗age抗体来中和。在接受血液透析治疗的糖尿病和终末期肾病患者（DM-HD）的血液循环中也发现了不同类型的AGE结构。我们通过凝胶过滤对正常对照和DM-HD患者的血清进行分离，鉴定出含有AGE表位- 1至-5和明确的AGE结构羧甲基赖氨酸（CML）的2个部分。这两个部分的加入导致培养的神经元细胞死亡，这种细胞毒性作用被添加抗age -2特异性抗体完全阻止。我们认为结构表位AGE-2是神经元细胞的一个重要的毒性片段。
The Maillard reaction that leads to the formation of advanced glycation end-products (AGEs) plays an important role in the pathogenesis of angiopathy in diabetic patients and in aging. AGEs are believed also to contribute to the pathology of Alzheimer disease (AD) and other neurodegenerative processes. Incubation of cortical neurons with 5 immunochemically distinct AGEs, designated AGEs-1 to -5, produced a dose-dependent increase in neuronal cell-death, as assessed by MTT assay, Trypan blue and Hoechst 33258 staining. The structural epitope designated AGE-2 was found to have the greatest cytopathic effect and the neurotoxicity of AGE-2 was neutralized by the addition of an anti AGE-2-specific antibody, but not by other types of anti-AGE antibodies. Distinct classes of AGE structures also have been established to circulate in the blood of individuals with diabetes mellitus and end-stage renal disease treated by hemodialysis (DM-HD). We fractionated serum from normal control and DM-HD patients by gel filtration and identified 2 fractions that contained AGE epitopes-l to -5 and as well as the defined AGE structure carboxymethyllysine (CML). The addition of these 2 fractions led to the death of cultured neuronal cells and this cytotoxic effect was completely prevented by the addition of the anti-AGE-2-specific antibody. We propose that the structural epitope AGE-2 is an important toxic moiety for neuronal cells.