II. CytochromeP-450 enzymes and oxidative stress
- 1 November 2001
- journal article
- research article
- Published by American Physiological Society in American Journal of Physiology-Gastrointestinal and Liver Physiology
- Vol. 281 (5) , G1135-G1139
- https://doi.org/10.1152/ajpgi.2001.281.5.g1135
Abstract
Oxidative stress is present in the liver of humans with steatosis and nonalcoholic steatohepatitis (NASH) and is a plausible mediator of cellular injury, inflammatory recruitment, and fibrogenesis. CYPs 2E1 and 4A are the microsomal oxidases involved with fatty acid oxidation. Both enzymes can reduce molecular oxygen to produce prooxidant species, which, if not countered efficiently by antioxidants, create oxidative stress. In this theme article, we present the evidence that, in the context of hepatic steatosis, CYPs 2E1 and 4A could generate the “second hit” of cellular injury, particularly when antioxidant reserves are depleted, and propose ways in which this could contribute to the pathogenesis of NASH.Keywords
This publication has 30 references indexed in Scilit:
- Removal of Glutathione Produces Apoptosis and Necrosis in HepG2 Cells Overexpressing CYP2E1Alcohol, Clinical and Experimental Research, 2001
- Induction of catalase, alpha, and microsomal glutathione S-transferase in CYP2E1 overexpressing HepG2 cells and protection against short-term oxidative stressHepatology, 2001
- Adenovirus-mediated Overexpression of Catalase in the Cytosolic or Mitochondrial Compartment Protects against Cytochrome P450 2E1-dependent Toxicity in HepG2 CellsPublished by Elsevier ,2001
- Ethanol and Arachidonic Acid Increase α2(I) Collagen Expression in Rat Hepatic Stellate Cells Overexpressing Cytochrome P450 2E1Journal of Biological Chemistry, 2000
- CYP2E1 and CYP4A as microsomal catalysts of lipid peroxides in murine nonalcoholic steatohepatitisJournal of Clinical Investigation, 2000
- Constitutive and Inducible Expression of Hepatic CYP2E1 in Leptin-deficient ob/ob MiceBiochemical and Biophysical Research Communications, 2000
- Altered Expression of HepaticCYP2E1andCYP4Ain Obese, Diabeticob/obMice, andfa/faZucker RatsBiochemical and Biophysical Research Communications, 1999
- Steatohepatitis: A tale of two “hits”?Gastroenterology, 1998
- Glu-320 and Asp-323 Are Determinants of the CYP4A1 Hydroxylation Regiospecificity and Resistance to Inactivation by 1-AminobenzotriazoleBiochemistry, 1998
- Increased hepatocyte CYP2E1 expression in a rat nutritional model of hepatic steatosis with inflammationGastroenterology, 1996