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Intracellular Toxic Advanced Glycation End-Products Promote the Production of Reactive Oxygen Species in HepG2 Cells
Hepatocyte cell death is a key process in the pathogenesis of nonalcoholic steatohepatitis (NASH). However, the factors responsible for and mechanisms underlying NASH-related cell death have not yet been elucidated in detail. We herein investigated the effects of intracellular glyceraldehyde (GA)-de...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402329/ https://www.ncbi.nlm.nih.gov/pubmed/32660150 http://dx.doi.org/10.3390/ijms21144861 |
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author | Sakasai-Sakai, Akiko Takata, Takanobu Takeuchi, Masayoshi |
author_facet | Sakasai-Sakai, Akiko Takata, Takanobu Takeuchi, Masayoshi |
author_sort | Sakasai-Sakai, Akiko |
collection | PubMed |
description | Hepatocyte cell death is a key process in the pathogenesis of nonalcoholic steatohepatitis (NASH). However, the factors responsible for and mechanisms underlying NASH-related cell death have not yet been elucidated in detail. We herein investigated the effects of intracellular glyceraldehyde (GA)-derived advanced glycation end-products (AGEs), named toxic AGEs (TAGE), on the production of reactive oxygen species (ROS), which have been implicated in the pathogenesis of NASH. Cell death related to intracellular TAGE accumulation was eliminated in the hepatocyte carcinoma cell line HepG2 by the antioxidant effects of N-acetyl-L-cysteine. The intracellular accumulation of TAGE increased ROS production and the expression of Nrf2, including its downstream gene. These results suggest that ROS are produced in association with the accumulation of TAGE and are a direct trigger for cell death. We also investigated the factors responsible for these increases in ROS. Catalase activity did not decrease with the accumulation of TAGE, while mitochondrial membrane depolarization was enhanced in cells treated with GA. These results indicate that TAGE play an important role in mitochondrial abnormalities and increases in ROS production, both of which are characteristic features of NASH. The suppression of TAGE accumulation has potential as a new therapeutic target in the progression of NASH. |
format | Online Article Text |
id | pubmed-7402329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-74023292020-08-07 Intracellular Toxic Advanced Glycation End-Products Promote the Production of Reactive Oxygen Species in HepG2 Cells Sakasai-Sakai, Akiko Takata, Takanobu Takeuchi, Masayoshi Int J Mol Sci Article Hepatocyte cell death is a key process in the pathogenesis of nonalcoholic steatohepatitis (NASH). However, the factors responsible for and mechanisms underlying NASH-related cell death have not yet been elucidated in detail. We herein investigated the effects of intracellular glyceraldehyde (GA)-derived advanced glycation end-products (AGEs), named toxic AGEs (TAGE), on the production of reactive oxygen species (ROS), which have been implicated in the pathogenesis of NASH. Cell death related to intracellular TAGE accumulation was eliminated in the hepatocyte carcinoma cell line HepG2 by the antioxidant effects of N-acetyl-L-cysteine. The intracellular accumulation of TAGE increased ROS production and the expression of Nrf2, including its downstream gene. These results suggest that ROS are produced in association with the accumulation of TAGE and are a direct trigger for cell death. We also investigated the factors responsible for these increases in ROS. Catalase activity did not decrease with the accumulation of TAGE, while mitochondrial membrane depolarization was enhanced in cells treated with GA. These results indicate that TAGE play an important role in mitochondrial abnormalities and increases in ROS production, both of which are characteristic features of NASH. The suppression of TAGE accumulation has potential as a new therapeutic target in the progression of NASH. MDPI 2020-07-09 /pmc/articles/PMC7402329/ /pubmed/32660150 http://dx.doi.org/10.3390/ijms21144861 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sakasai-Sakai, Akiko Takata, Takanobu Takeuchi, Masayoshi Intracellular Toxic Advanced Glycation End-Products Promote the Production of Reactive Oxygen Species in HepG2 Cells |
title | Intracellular Toxic Advanced Glycation End-Products Promote the Production of Reactive Oxygen Species in HepG2 Cells |
title_full | Intracellular Toxic Advanced Glycation End-Products Promote the Production of Reactive Oxygen Species in HepG2 Cells |
title_fullStr | Intracellular Toxic Advanced Glycation End-Products Promote the Production of Reactive Oxygen Species in HepG2 Cells |
title_full_unstemmed | Intracellular Toxic Advanced Glycation End-Products Promote the Production of Reactive Oxygen Species in HepG2 Cells |
title_short | Intracellular Toxic Advanced Glycation End-Products Promote the Production of Reactive Oxygen Species in HepG2 Cells |
title_sort | intracellular toxic advanced glycation end-products promote the production of reactive oxygen species in hepg2 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402329/ https://www.ncbi.nlm.nih.gov/pubmed/32660150 http://dx.doi.org/10.3390/ijms21144861 |
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