Intracellular Toxic Advanced Glycation End-Products Promote the Production of Reactive Oxygen Species in HepG2 Cells
Autor: | Masayoshi Takeuchi, Takanobu Takata, Akiko Sakasai-Sakai |
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Rok vydání: | 2020 |
Předmět: |
Glycation End Products
Advanced 0301 basic medicine Antioxidant glyceraldehyde (GA) medicine.medical_treatment advanced glycation end-products (AGEs) lcsh:Chemistry chemistry.chemical_compound 0302 clinical medicine Non-alcoholic Fatty Liver Disease Glycation Glyceraldehyde nonalcoholic steatohepatitis (NASH) toxic AGEs (TAGE) lcsh:QH301-705.5 nonalcoholic fatty liver disease (NAFLD) Spectroscopy Membrane Potential Mitochondrial chemistry.chemical_classification Cell Death biology Chemistry Liver Neoplasms Hep G2 Cells General Medicine Mitochondria Computer Science Applications Cell biology medicine.anatomical_structure Catalase 030220 oncology & carcinogenesis Hepatocyte Disease Progression Intracellular Programmed cell death Carcinoma Hepatocellular NF-E2-Related Factor 2 reactive oxygen species (ROS) Article glyceraldehyde-derived AGEs Catalysis Inorganic Chemistry 03 medical and health sciences Cell Line Tumor medicine Humans Physical and Theoretical Chemistry Molecular Biology Reactive oxygen species Organic Chemistry 030104 developmental biology lcsh:Biology (General) lcsh:QD1-999 Hepatocytes biology.protein Reactive Oxygen Species |
Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 14 International Journal of Molecular Sciences, Vol 21, Iss 4861, p 4861 (2020) |
ISSN: | 1422-0067 |
Popis: | 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. |
Databáze: | OpenAIRE |
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