The Effect of Glyceraldehyde-Derived Advanced Glycation End Products on β-Tubulin-Inhibited Neurite Outgrowth in SH-SY5Y Human Neuroblastoma Cells.
The Effect of Glyceraldehyde-Derived Advanced Glycation End Products on β-Tubulin-Inhibited Neurite Outgrowth in SH-SY5Y Human Neuroblastoma Cells.
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DOI：
10.3390/nu12102958
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发表时间：
2020-09-27
期刊：
影响因子：
5.9
通讯作者：
Koriyama Y
中科院分区：
文献类型：
--
作者：
Nasu R;Furukawa A;Suzuki K;Takeuchi M;Koriyama Y
营养因素会影响神经系统疾病的风险及其进展速度。特别地，糖尿病患者中碳水化合物代谢的异常导致神经障碍如阿尔茨海默病（AD）的风险增加。本研究采用甘油醛（glyceraldehyde，GA）处理SH-SY 5 Y神经母细胞瘤细胞，探讨神经系统紊乱与AD发病机制的关系。我们先前报道了GA衍生的毒性晚期糖基化终产物（毒性AGEs，TAGE）诱导AD样改变，包括细胞内tau蛋白磷酸化。然而，TAGE及其靶分子在AD发病机制中的作用仍不清楚。在这项研究中，我们通过使用抗TAGE抗体进行二维免疫印迹分析和质谱分析来研究TAGE的靶蛋白，并将β-微管蛋白鉴定为靶蛋白之一。GA处理诱导SH-SY 5 Y细胞TAGE-β-tubulin形成和β-tubulin异常聚集，并抑制神经突起生长。另一方面，葡萄糖源性AGEs也参与了AD的发生。而葡萄糖不引起β-微管蛋白的异常聚集，也不抑制神经突起的生长。了解GA形成TAGE-β-微管蛋白的潜在机制及其在神经变性中的作用可能有助于开发新的治疗和神经保护策略。
Nutritional factors can affect the risk of developing neurological disorders and their rate of progression. In particular, abnormalities of carbohydrate metabolism in diabetes mellitus patients lead to an increased risk of neurological disorders such as Alzheimer’s disease (AD). In this study, we investigated the relationship between nervous system disorder and the pathogenesis of AD by exposing SH-SY5Y neuroblastoma cells to glyceraldehyde (GA). We previously reported that GA-derived toxic advanced glycation end products (toxic AGEs, TAGE) induce AD-like alterations including intracellular tau phosphorylation. However, the role of TAGE and their target molecules in the pathogenesis of AD remains unclear. In this study, we investigated the target protein for TAGE by performing two-dimensional immunoblot analysis with anti-TAGE antibody and mass spectrometry and identified β-tubulin as one of the targets. GA treatment induced TAGE-β-tubulin formation and abnormal aggregation of β-tubulin, and inhibited neurite outgrowth in SH-SY5Y cells. On the other hand, glucose-derived AGEs were also involved in developing AD. However, glucose did not make abnormal aggregation of β-tubulin and did not inhibit neurite outgrowth. Understanding the underlying mechanism of TAGE-β-tubulin formation by GA and its role in neurodegeneration may aid in the development of novel therapeutics and neuroprotection strategies.
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影响因子：
5.7
作者：
Takeuchi, M;Makita, Z;Koike, T
通讯作者：
Koike, T
影响因子：
4.7
作者：
Takeuchi, M;Yamagishi, S
通讯作者：
Yamagishi, S
DOI：
10.1097/01.wcb.0000090622.86921.0e
发表时间：
2003-11-01
影响因子：
6.3
作者：
de Arriba, SG;Loske, C;Münch, G
通讯作者：
Münch, G
影响因子：
16.2
作者：
Tahara N;Yamagishi S;Takeuchi M;Honda A;Tahara A;Nitta Y;Kodama N;Mizoguchi M;Kaida H;Ishibashi M;Hayabuchi N;Matsui T;Imaizumi T
通讯作者：
Imaizumi T
影响因子：
2.1
作者：
Takeuchi, Masayoshi;Kikuchi, Seiji;Yamagishi, Sho-ichi
通讯作者：
Yamagishi, Sho-ichi