CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload

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Harjumäki , R , Pridgeon , C S & Ingelman-Sundberg , M 2021 , ' CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload ' , International Journal of Molecular Sciences , vol. 22 , no. 15 , 8221 . https://doi.org/10.3390/ijms22158221

Title: CYP2E1 in Alcoholic and Non-Alcoholic Liver Injury. Roles of ROS, Reactive Intermediates and Lipid Overload
Author: Harjumäki, Riina; Pridgeon, Chris S.; Ingelman-Sundberg, Magnus
Other contributor: University of Helsinki, Division of Pharmaceutical Biosciences


Date: 2021-08
Language: eng
Number of pages: 20
Belongs to series: International Journal of Molecular Sciences
ISSN: 1422-0067
DOI: https://doi.org/10.3390/ijms22158221
URI: http://hdl.handle.net/10138/333308
Abstract: CYP2E1 is one of the fifty-seven cytochrome P450 genes in the human genome and is highly conserved. CYP2E1 is a unique P450 enzyme because its heme iron is constitutively in the high spin state, allowing direct reduction of, e.g., dioxygen, causing the formation of a variety of reactive oxygen species and reduction of xenobiotics to toxic products. The CYP2E1 enzyme has been the focus of scientific interest due to (i) its important endogenous function in liver homeostasis, (ii) its ability to activate procarcinogens and to convert certain drugs, e.g., paracetamol and anesthetics, to cytotoxic end products, (iii) its unique ability to effectively reduce dioxygen to radical species causing liver injury, (iv) its capability to reduce compounds, often generating radical intermediates of direct toxic or indirect immunotoxic properties and (v) its contribution to the development of alcoholic liver disease, steatosis and NASH. In this overview, we present the discovery of the enzyme and studies in humans, 3D liver systems and genetically modified mice to disclose its function and clinical relevance. Induction of the CYP2E1 enzyme either by alcohol or high-fat diet leads to increased severity of liver pathology and likelihood to develop ALD and NASH, with subsequent influence on the occurrence of hepatocellular cancer. Thus, fat-dependent induction of the enzyme might provide a link between steatosis and fibrosis in the liver. We conclude that CYP2E1 has many important physiological functions and is a key enzyme for hepatic carcinogenesis, drug toxicity and liver disease.
Subject: NASH
NAFLD
liver
ROS
NAFL
lipid peroxidation
HUMAN CYTOCHROME-P450 2E1
ETHANOL-OXIDIZING SYSTEM
INDUCED GUT LEAKINESS
FATTY LIVER
OXIDATIVE STRESS
RAT-LIVER
HALOTHANE METABOLISM
MICROSOMAL CYTOCHROME-P-450
INDUCIBLE CYTOCHROME-P-450
MITOCHONDRIAL DYSFUNCTION
1182 Biochemistry, cell and molecular biology
3111 Biomedicine
317 Pharmacy
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