title: CYP2E1, oxidative stress, post-translational modifications and lipid metabolism.
abstract: Chronic alcohol-mediated down-regulation of hepatic ST6Gal1 gene leads to defective glycosylation of lipid-carrying apolipoproteins such as apo E and apo J, resulting in defective VLDL assembly and intracellular lipid and lipoprotein transport, which in turn is responsible for alcoholic hepatosteatosis and ALD. The mechanism of ethanol action involves thedepletion of a unique RNA binding protein that specifically interacts with its 3'-UTR region of ST6Gal1 mRNA resulting in its destabilization and consequent appearance of asialoconjugates as alcohol biomarkers. With respect to ETOH effects on Cardio-Vascular Diseases, we conclude that CYP2E1 and ETOH mediated oxidative stress significantly down regulates not only the hepatic PON1 gene expression, but also serum PON1 and HCTLase activities accompanied by depletion of hepatic GSH, the endogenous antioxidant. These results strongly implicate the susceptibility of PON1 to increased ROS production. In contrast, betaine seems to be both hepatoprotective and atheroprotective by reducing hepatosteatosis and restoring not only liver GSH that quenches free radicals, but also the antiatherogenic PON1 gene expression and activity.
authors: Department of Biochemistry and Molecular Biology, The George Washington University, Washington, DC, USA, Raj.Lakshman@va.gov.
authors: M Raj
authors: MR
authors: Lakshman
authors: Mamatha
authors: M
authors: Garige
authors: Maokai A
authors: MA
authors: Gong
authors: Leslie
authors: L
authors: Leckey
authors: Ravi
authors: R
authors: Varatharajalu
authors: Robert S
authors: RS
authors: Redman
authors: Devanshi
authors: D
authors: Seth
authors: Paul S
authors: PS
authors: Haber
authors: Kenneth
authors: K
authors: Hirsch
authors: Richard
authors: R
authors: Amdur
authors: Ruchi
authors: R
authors: Shah
mesh_terms: D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism*; D006801:Humans; D050356:Lipid Metabolism; D008107:Liver Diseases / Q000201:enzymology / Q000473:pathology*; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational
chemical_list: D019392:Cytochrome P-450 CYP2E1