Intracellular Toxic AGEs (TAGE) Triggers Numerous Types of Cell Damage

Abstract

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.

The Association between Accumulation of Toxic Advanced Glycation End-Products and Cytotoxic Effect in MC3T3-E1 Cells

“…Based on these findings, we refer to the AGEs recognized by the anti-TAGE antibody as toxic AGEs (TAGE). Increased TAGE levels were found to correlate with various lifestyle diseases, such as non-alcoholic steatohepatitis, DM, cancer, dementia, infertility, and cardiovascular diseases [ 22 , 23 , 24 ]. An analysis of the toxicity of TAGE in the liver, a major site for the metabolism of excess glucose and fructose, revealed that the accumulation of TAGE was associated with damage to cell function and the induction of cell death, ultimately leading to liver disease [ 25 , 26 , 27 , 28 ].…”

Glycation damage to organelles and their DNA increases during maize seedling development

“…www.nature.com/scientificreports/ Defense against glycation damage in mitochondria and plastids. The glycating agents MGO and GO are produced spontaneously during sugar metabolism and lipid peroxidation, so that all organisms need to defend against the ensuing damage 34,35 . The main pathway of MGO detoxification is the glyoxalase system comprised of glyoxalases 1 and 2 (I and II in plants) and glutathione 36,37 .…”

AGEs-Induced and Endoplasmic Reticulum Stress/Inflammation-Mediated Regulation of GLUT4 Expression and Atherogenesis in Diabetes Mellitus

“…Increased consumption of sugars, especially fructose, and AGE-enriched diets are related to the generation of intracellular AGEs that induce lipogenesis and inflammation in crosstalk with ER stress [ 125 ]. Besides, the extravasation of AGEs and its interaction with RAGE is associated with the development and evolution of several chronic diseases, including steatosis and CVD [ 126 ]. A recent meta-analysis found an association among elevated levels of several types of AGEs with NAFLD [ 127 ] and the determination of fluorescent AGE has been considered as a potential biomarker for NAFLD stratification [ 128 ].…”