Intracellular Toxic Advanced Glycation End-Products Promote the Production of Reactive Oxygen Species in HepG2 Cells

Autor: Masayoshi Takeuchi, Takanobu Takata, Akiko Sakasai-Sakai
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
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje