Intracellular Toxic AGEs (TAGE) Triggers Numerous Types of Cell Damage.
Intracellular Toxic AGEs (TAGE) Triggers Numerous Types of Cell Damage.
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DOI：
10.3390/biom11030387
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发表时间：
2021-03-05
期刊：
影响因子：
5.5
通讯作者：
Matsunaga T
中科院分区：
文献类型：
--
作者：
Takeuchi M;Sakasai-Sakai A;Takata T;Takino JI;Koriyama Y;Kikuchi C;Furukawa A;Nagamine K;Hori T;Matsunaga T
大量糖的习惯性摄入与生活方式相关疾病（LSRD）的发病/进展有关，其诱导神经元细胞、肝细胞和心肌细胞中糖代谢中间体甘油醛（GA）的过量产生。GA和细胞内蛋白质之间的反应产生毒性晚期糖基化终产物（毒性AGEs，TAGE），其积累有助于各种疾病，如阿尔茨海默病、非酒精性脂肪性肝炎和心血管疾病。TAGE的细胞渗漏通过AGEs受体（AGEs）影响周围细胞，从而促进LSRD的发作/进展。我们证明了TAGE的细胞内积累引发了许多细胞疾病，并且TAGE泄漏到细胞外空间，从而增加循环液中的细胞外TAGE水平。细胞内信号传导和活性氧的产生受到细胞外TAGE和TAGE相互作用的影响，这反过来又促进了TAGE的细胞内生成，所有这些都可能有助于在LSRD中观察到的病理变化。在这篇综述中，我们讨论了细胞内TAGE水平和多种类型的细胞损伤之间的关系。TAGE理论的提出为LSRD的研究开辟了新的视角。
The habitual intake of large amounts of sugar, which has been implicated in the onset/progression of lifestyle-related diseases (LSRD), induces the excessive production of glyceraldehyde (GA), an intermediate of sugar metabolism, in neuronal cells, hepatocytes, and cardiomyocytes. Reactions between GA and intracellular proteins produce toxic advanced glycation end-products (toxic AGEs, TAGE), the accumulation of which contributes to various diseases, such as Alzheimer’s disease, non-alcoholic steatohepatitis, and cardiovascular disease. The cellular leakage of TAGE affects the surrounding cells via the receptor for AGEs (RAGE), thereby promoting the onset/progression of LSRD. We demonstrated that the intracellular accumulation of TAGE triggered numerous cellular disorders, and also that TAGE leaked into the extracellular space, thereby increasing extracellular TAGE levels in circulating fluids. Intracellular signaling and the production of reactive oxygen species are affected by extracellular TAGE and RAGE interactions, which, in turn, facilitate the intracellular generation of TAGE, all of which may contribute to the pathological changes observed in LSRD. In this review, we discuss the relationships between intracellular TAGE levels and numerous types of cell damage. The novel concept of the “TAGE theory” is expected to open new perspectives for research into LSRD.
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影响因子：
9.3
作者：
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作者：
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通讯作者：
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