Chronic ethanol treatment depletes glutathione regeneration capacity in hepatoma cell line HepG2
Autor: | Jan-Heiner Küpper, Natalie Herzog, Kai-Uwe Schmidtke, S. Kade |
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Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
chemistry.chemical_classification Reactive oxygen species Ethanol Antioxidant biology Chemistry medicine.medical_treatment Acetaldehyde Glutathione CYP2E1 Pharmacology Applied Microbiology and Biotechnology 03 medical and health sciences chemistry.chemical_compound 030104 developmental biology 0302 clinical medicine Biochemistry 030220 oncology & carcinogenesis biology.protein medicine Molecular Biology Intracellular Biotechnology Alcohol dehydrogenase |
Zdroj: | Journal of Cellular Biotechnology. 1:183-190 |
ISSN: | 2352-3697 2352-3689 |
Popis: | Chronic alcohol abuse is the leading cause of liver cirrhosis in western countries. Ethanol, even at lower concentrations, can cause pleiotropic effects at the cellular level such as the formation of reactive oxygen species (ROS) and DNA damage. Ethanol is oxidized to acetaldehyde by liver alcohol dehydrogenase and by a microsomal ethanol-oxidizing system which is dependent on CYP2E1. There are numerous reports on CYP2E1-mediated formation of ROS. These lower the levels of intracellular glutathione, an efficient antioxidant. We were interested to investigate ethanol effects on glutathione levels independent of CYP2E1. We chose human hepatoma cell line HepG2 as a model known to lack physiological CYP2E1 expression. We found that 40 mM ethanol, a dosage comparable to blood ethanol concentration after heavy alcohol drinking, reduced intracellular HepG2 glutathione levels only by 18%. Within 24 hours, this effect could be normalized by the glutathione regeneration system. When HepG2 cells were exposed to 40 mM ethanol for one week, the cells gradually lost their ability to regenerate intracellular glutathione stores. We conclude that chronic ethanol exposure has a substantial effect on the glutathione regeneration capacity in liver cells which might contribute to alcohol-induced liver disease. |
Databáze: | OpenAIRE |
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