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Involvement of Intracellular TAGE and the TAGE–RAGE–ROS Axis in the Onset and Progression of NAFLD/NASH
The repeated excessive intake of sugar, a factor that contributes to the onset of nonalcoholic fatty liver disease (NAFLD) and its progression to the chronic form of nonalcoholic steatohepatitis (NASH), markedly increases the hepatocyte content of glyceraldehyde (GA), a glucose/fructose metabolic in...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045097/ https://www.ncbi.nlm.nih.gov/pubmed/36978995 http://dx.doi.org/10.3390/antiox12030748 |
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author | Sakasai-Sakai, Akiko Takeda, Kenji Takeuchi, Masayoshi |
author_facet | Sakasai-Sakai, Akiko Takeda, Kenji Takeuchi, Masayoshi |
author_sort | Sakasai-Sakai, Akiko |
collection | PubMed |
description | The repeated excessive intake of sugar, a factor that contributes to the onset of nonalcoholic fatty liver disease (NAFLD) and its progression to the chronic form of nonalcoholic steatohepatitis (NASH), markedly increases the hepatocyte content of glyceraldehyde (GA), a glucose/fructose metabolic intermediate. Toxic advanced glycation end-products (toxic AGEs, TAGE) are synthesized by cross-linking reactions between the aldehyde group of GA and the amino group of proteins, and their accumulation has been implicated in the development of NAFLD/NASH and hepatocellular carcinoma (HCC). Our previous findings not only showed that hepatocyte disorders were induced by the intracellular accumulation of TAGE, but they also indicated that extracellular leakage resulted in elevated TAGE concentrations in circulating fluids. Interactions between extracellular TAGE and receptor for AGEs (RAGE) affect intracellular signaling and reactive oxygen species (ROS) production, which may, in turn, contribute to the pathological changes observed in NAFLD/NASH. RAGE plays a role in the effects of the extracellular leakage of TAGE on the surrounding cells, which ultimately promote the onset and progression of NAFLD/NASH. This review describes the relationships between intracellular TAGE levels and hepatocyte and hepatic stellate cell (HSC) damage as well as the TAGE–RAGE–ROS axis in hepatocytes, HSC, and HCC cells. The “TAGE theory” will provide novel insights for future research on NAFLD/NASH. |
format | Online Article Text |
id | pubmed-10045097 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100450972023-03-29 Involvement of Intracellular TAGE and the TAGE–RAGE–ROS Axis in the Onset and Progression of NAFLD/NASH Sakasai-Sakai, Akiko Takeda, Kenji Takeuchi, Masayoshi Antioxidants (Basel) Review The repeated excessive intake of sugar, a factor that contributes to the onset of nonalcoholic fatty liver disease (NAFLD) and its progression to the chronic form of nonalcoholic steatohepatitis (NASH), markedly increases the hepatocyte content of glyceraldehyde (GA), a glucose/fructose metabolic intermediate. Toxic advanced glycation end-products (toxic AGEs, TAGE) are synthesized by cross-linking reactions between the aldehyde group of GA and the amino group of proteins, and their accumulation has been implicated in the development of NAFLD/NASH and hepatocellular carcinoma (HCC). Our previous findings not only showed that hepatocyte disorders were induced by the intracellular accumulation of TAGE, but they also indicated that extracellular leakage resulted in elevated TAGE concentrations in circulating fluids. Interactions between extracellular TAGE and receptor for AGEs (RAGE) affect intracellular signaling and reactive oxygen species (ROS) production, which may, in turn, contribute to the pathological changes observed in NAFLD/NASH. RAGE plays a role in the effects of the extracellular leakage of TAGE on the surrounding cells, which ultimately promote the onset and progression of NAFLD/NASH. This review describes the relationships between intracellular TAGE levels and hepatocyte and hepatic stellate cell (HSC) damage as well as the TAGE–RAGE–ROS axis in hepatocytes, HSC, and HCC cells. The “TAGE theory” will provide novel insights for future research on NAFLD/NASH. MDPI 2023-03-19 /pmc/articles/PMC10045097/ /pubmed/36978995 http://dx.doi.org/10.3390/antiox12030748 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Sakasai-Sakai, Akiko Takeda, Kenji Takeuchi, Masayoshi Involvement of Intracellular TAGE and the TAGE–RAGE–ROS Axis in the Onset and Progression of NAFLD/NASH |
title | Involvement of Intracellular TAGE and the TAGE–RAGE–ROS Axis in the Onset and Progression of NAFLD/NASH |
title_full | Involvement of Intracellular TAGE and the TAGE–RAGE–ROS Axis in the Onset and Progression of NAFLD/NASH |
title_fullStr | Involvement of Intracellular TAGE and the TAGE–RAGE–ROS Axis in the Onset and Progression of NAFLD/NASH |
title_full_unstemmed | Involvement of Intracellular TAGE and the TAGE–RAGE–ROS Axis in the Onset and Progression of NAFLD/NASH |
title_short | Involvement of Intracellular TAGE and the TAGE–RAGE–ROS Axis in the Onset and Progression of NAFLD/NASH |
title_sort | involvement of intracellular tage and the tage–rage–ros axis in the onset and progression of nafld/nash |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10045097/ https://www.ncbi.nlm.nih.gov/pubmed/36978995 http://dx.doi.org/10.3390/antiox12030748 |
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