Cytochrome P450 2E1: Its Role in Disease and Drug Metabolism (eBook)

List of Contributors.- Preface.- Acknowledgements.- Chapter 1 Cytochrome P450 2E1 and its clinical aspects: an introduction and a brief perspective on the current research scenario, Aparajita Dey.- 1.1 Introduction.- 1.1.1 Purification and characterization of CYP2E1.- 1.1.2 The role of CYP2E1 as a potent source for oxidative stress.- 1.1.3 CYP2E1 and ethanol-mediated oxidative stress.- 1.1.4 Importance of CYP2E1 in health and disease.- 1.2 Research studies elucidating the role of CYP2E1 in disease and drug metabolism.- 1.3 Conclusions.- Chapter 2 Nrf2 and antioxidant defense against CYP2E1 toxicity, Arthur I Cederbaum.- 2.1 Introduction.- 2.2 Systems Producing ROS.- 2.2.1 Protection against ROS toxicity.- 2.2.2 Alcohol, oxidative stress, and cell injury.- 2.3 CYP2E1.- 2.3.1 CYP2E1 and alcohol-induced liver injury.- 2.3.2 Biochemical and toxicological properties of CYP2E1 in HepG2 cells.- 2.3.3 Upregulation of antioxidant defense in CYP2E1 expressing liver cells.- 2.4 Nrf2 Signaling.- 2.4.1 Nrf2 and CYP2E1-induced toxicity.- 2.4.2 Nrf2 protects HepG2 cells against CYP2E1 plus arachidonic acid toxicity.- 2.4.3 Nrf2 and ethanol-induced toxicity.- 2.5 Conclusions.- Chapter 3 The role of Cytochrome P-4502E1 in ethanol-mediated carcinogenesis, Helmut K Seitz and Xiang-Dong Wang.- 3.1 Introduction.- 3.2 Induction and inhibition of CYP2E1.- 3.3 Activation of procarcinogens via CYP2E1.- 3.4 Generation of ROS through ethanol metabolism via CYP2E1.- 3.5 The role of CYP2E1 in the metabolism of retinoids and their importance in carcinogenesis.- 3.6 The role of CYP2E1 in chemically induced hepatocarcinogenesis.- 3.7 Summary and Conclusion.- Chapter 4 The Importance of CYP2E1 in the pathogenesis of alcoholic liver disease and drug toxicity and the role of the proteasome, SW French.- 4.1 Introduction.- 4.2 The role of CYP2E1 in liver damage caused by ethanol.- 4.2.1 Hydroxyethyl radicals generated by CYP2E1/ethanol metabolism: significance in ethanol hepatotoxicity.- 4.3 The pathogenesis of liver pathology due to alcohol-induced CYP2E1.- 4.4 Drug hepatitis involving drugs that are metabolized by CYP2E1 when CYP2E1 has been induced by ethanol ingestion.- 4.5 CYP2E1 induction: effect on epigenetic expression.- 4.6 Role of the proteasome in CYP2E1 stabilization.- 4.7 Role of CYP2E1 in drug cholestatic hepatitis (DDC) plus ethanol.- 4.8 Role of CYP2E1 in non-alcoholic hepatitis (NASH).- 4.9 CYP2E1 polymorphism and genetic links to alcoholic liver disease.- 4.10 Conclusions.- Chapter 5 Relevance of CYP2E1 to non-alcoholic fatty liver disease, Ann K Daly.- 5.1 Introduction.- 5.2 CYP2E1 and NAFLD.- 5.3 Genetics of NAFLD including possible role of CYP2E1 polymorphisms.- 5.3.1 Background.- 5.3.2 Candidate gene studies on NAFLD.- 5.3.3 Candidate gene studies on CYP2E1 as a genetic risk factor in NAFLD.- 5.3.4 Genome-wide association studies on NAFLD.- 5.4 Concluding remarks.- Chapter 6 CYP2E1-catalyzed alcohol metabolism: role of oxidant generation in interferon signaling, antigen presentation and autophagy, Natalia A. Osna and Terrence M. Donohue Jr.- 6.1 CYP2E1 regulation by ethanol exposure.- 6.1.1 Hepatic ethanol oxidation in the liver.- 6.1.2 Induction of CYP2E1 by ethanol.- 6.2. Oxidant generation and interferon signaling.- 6.3 Proteasome activity and CYP2E1: reciprocal regulation by IFNγ and ethanol.- 6.4 Interferon-dependent antigen processing and presentation in liver cells.- 6.5 Involvement of CYP2E1 in the ethanol-induced regulation of autophagy.- 6.5.1 Physiological function of autophagy.- 6.5.2 Autophagy in liver during alcohol consumption.- 6.5.3 Alcohol-induced fatty liver.- 6.5.4 Interferon-induced autophagy.- 6.6. Summary and future directions.- Chapter 7 CYP2E1, oxidative stress, post-translational modifications and  lipid metabolism, MR Lakshmanan.- 7.1 Introduction.- 7.2 Ethical guideline and alcoholic specimen criteria.- 7.3.1 Ethanol per se, not other liver pathological conditions, mediates the down-regulation of ST6Gal1 gene.- 7.3.2 Liver lipid deposition directly correlates with the amount of alcohol consumed.- 7.3.3Alcohol consumption correlates positively with hepatic steatosis.- 7.3.4 Strong multivariate relationships exist between alcohol-drinking history, ST6Gal1 gene expression, and liver lipid deposits.- 7.3.5 Expression of CYP2E1 and ADH in the respective HepG2 cell lines.- 7.3.6 Effect of ethanol on ST6Gal1 mRNA expression in CYP2E1 cells.- 7.3.7 Effect of ethanol on ST6Gal1 mRNA expression in HAD liver cells.- 7.3.8 Effect of ethanol and acetaldehyde on ST6Gal1 mRNA expression in wild-type HepG2 liver cells.- 7.3.9 Effect of HNE on ST6Gal1 mRNA expression in CYP2E1 cells.- 7.3.10 Partial identification of the liver cytosol protein that forms complex with the 3'-UTR of Rat ST6Gal1 mRNA.- 7.3.11 Importance of secondary structure of RNA in RNA-Protein Complex Formation.- 7.3.12 The RNA-Protein interaction protects 3'-UTR from RNase digestion.- 7.3.13 Partial characterization of protein interacting with 3'-UTR of ST6Gal1 mRNA by UV cross-linking.- 7.3.14 Thirteen-base pair motif of ST6Gal1 mRNA is suffi­cient for the specific protein to bind.- 7.3.15 The specificity of the cytosolic binding protein that interacts with ST6Gal1 mRNA.- 7.3.16 Effects of chronic ethanol exposure in vivo on the status of the binding protein.- 7.3.17 Influence of chronic ethanol and betaine on animal body and liver weights.- 7.3.18  Influence of chronic ethanol and betaine liver PON1 mRNA expression in rats fed low and high ω-3 PUFA diets.- 7.3.19 Influence of chronic ethanol and betaine on serum PON1 and HCTLase activities in rats fed low and high ω-3 PUFA diets.- 7.3.20 Influence of chronic ethanol, ω-3 PUFA and betaine on liver GSH levels in rats fed low and high ω-3 PUFA diets.- 7.3.21 Influence of chronic ethanol, ω-3 PUFA and betaine on serum ALT.- 7.3.22 Influence of chronic ethanol, ω-3 PUFA and betaine on liver lipid score.- 7.4 Significance of the results.- 7.5 Conclusions.- Chapter 8 The role of CYP2E1 in alcohol metabolism and sensitivity in the central nervous system, V.Vasiliou.- 8.1 Introduction.- 8.2 Ethanol metabolism in the CNS.- 8.3 Acetaldehyde in ethanol sensitivity of the brain.- 8.4 Acetaldehyde production in the brain.- 8.5 CYP2E1 expression in the brain.- 8.6 Regulation of CYP2E1 in the CNS.- 8.6 Regulation of CYP2E1 in the CNS.- 8.7 Genetic variation of CYP2E1 in ethanol sensitivity.- 8.8 Conclusion. Index.