TAGE (toxic AGEs) hypothesis in various chronic diseases
TAGE (toxic AGEs) hypothesis in various chronic diseases
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DOI：
10.1016/j.mehy.2004.02.042
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发表时间：
2004-01-01
影响因子：
4.7
通讯作者：
Yamagishi, S
中科院分区：
文献类型：
--
作者：
Takeuchi, M;Yamagishi, S
糖基化过程的晚期阶段（蛋白质翻译后修饰的一种）导致晚期糖基化终产物（AGEs）的形成，并在糖尿病患者血管病变、衰老和神经退行性疾病的发病机制中发挥重要作用。然而，目前尚不清楚哪些AGEs亚型起发病作用，以及几种AGEs受体中哪一种介导了AGEs对细胞的作用。我们已经提供了直接的免疫化学证据，证明在糖尿病患者血清中循环的AGEs修饰蛋白和肽中存在六种不同的AGEs结构（AGEs-1至-6）。最近，我们首次证明了甘油醛衍生的AGEs （AGEs-2）和乙醇醛衍生的AGEs （AGE-3）对血管壁细胞、系膜细胞、雪旺细胞、恶性黑色素瘤细胞和皮质神经元具有不同的生物活性。我们还首次证明了乙醛（AA）衍生的AGEs （AA- age）对皮质神经元具有细胞毒性活性，并且在酗酒者的人脑中检测到AA- age表位。这些结果表明，在体内可形成的各种AGEs结构中，毒性AGEs （age）结构（AGEs 2、3和AA-AGE）可能在与AGEs形成相关的病理生理过程中起重要作用，而非无毒AGEs （n -羧甲基赖氨酸、戊苷、吡啶等）可能在AGEs形成相关的病理生理过程中起重要作用。(C) 2004 Elsevier Ltd.版权所有。
The advanced stage of the glycation process (one of the post-translational modifications of proteins) leads to the formation of advanced glycation end-products (AGEs) and plays an important role in the pathogenesis of angiopathy in diabetic patients, in aging, and in neurodegenerative diseases. However, it is still not clear which AGEs subtypes play a pathogenetic role and which of several AGEs receptor mediate AGEs effects on cells. We have provided direct immunochemical evidence for the existence of six distinct AGEs structures (AGEs-1 to -6) within the AGEs-modified proteins and peptides that circulate in the serum of diabetic patients. Recently we demonstrated for the first time that glyceraldehyde-derived AGEs (AGEs-2) and glycolaldehyde-derived AGEs (AGE-3) have diverse biological activities on vascular wall cells, mesangial cells, Schwann cells, malignant melanoma cells and cortical neurons. We also demonstrated for the first time that acetaldehyde (AA)-derived AGEs (AA-AGE) have cytotoxic activity on cortical neurons and the AA-AGE epitope was detected in human brain of alcoholics. These results indicate that of the various types of AGEs structures that can form in vivo, the toxic AGEs (TAGE) structures (AGEs 2, 3, and AA-AGE), but not nontoxic AGEs (N-carboxymethyllysine, pentosidine, pyrraline etc.) are likely to play an important rote in the pathophysiological processes associated with AGEs formation. (C) 2004 Elsevier Ltd. All rights reserved.