Linked Life Data

16374848

Source:http://linkedlifedata.com/resource/pubmed/id/16374848

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-12-28
pubmed:abstractText
Induction of CYP2E1 by ethanol is one pathway through which ethanol generates oxidative stress. Nrf2 is a transcription factor that regulates important antioxidant and phase II detoxification genes. Nrf2 induction by CYP2E1 and its importance in the adaptive response to increased oxidative stress caused by CYP2E1 was studied. Increases in Nrf2 protein and mRNA were observed in livers or hepatocytes of chronic alcohol-fed mice or rats and of pyrazole-treated rats or mice, conditions known to elevate CYP2E1. HepG2 cells expressing CYP2E1 (E47 cells) showed increased Nrf2 mRNA and protein expression compared with control HepG2 C34 cells. Nrf2 is activated in E47 cells as shown by an increase in nuclear Nrf2 levels and Nrf2-antioxidant-responsive element binding activity, and upregulation of Nrf2-regultated genes, glutamate cysteine ligase catalytic subunit (GCLC), and heme oxygenase 1 (HO-1). Increases in Nrf2 protein and mRNA are blocked by inhibitors of CYP2E1 activity and a reactive oxygen species (ROS) scavenger, N-acetylcysteine, which decrease ROS levels as well as Nrf2 mRNA induction. Upregulation of GCLC and HO-1 in E47 cells is dependent on Nrf2 and is prevented by siRNA-Nrf2. Blocking Nrf2 by siRNA-Nrf2 decreases glutathione and increases ROS and lipid peroxidation, resulting in decreased mitochondrial membrane potential and loss of cell viability of E47 cells but not C34 cells. These results suggest that Nrf2 is activated and that levels of protein and mRNA are increased when CYP2E1 is elevated. In conclusion, Nrf2 plays a key role in the adaptive response against increased oxidative stress caused by CYP2E1.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
144-53
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16374848-Animals, pubmed-meshheading:16374848-Cell Survival, pubmed-meshheading:16374848-Cells, Cultured, pubmed-meshheading:16374848-Cytochrome P-450 CYP2E1, pubmed-meshheading:16374848-Ethanol, pubmed-meshheading:16374848-Glutamate-Cysteine Ligase, pubmed-meshheading:16374848-Heme Oxygenase-1, pubmed-meshheading:16374848-Liver, pubmed-meshheading:16374848-Male, pubmed-meshheading:16374848-Membrane Potentials, pubmed-meshheading:16374848-Mice, pubmed-meshheading:16374848-Mice, Inbred C57BL, pubmed-meshheading:16374848-NF-E2-Related Factor 2, pubmed-meshheading:16374848-Oxidative Stress, pubmed-meshheading:16374848-Pyrazoles, pubmed-meshheading:16374848-RNA, Messenger, pubmed-meshheading:16374848-RNA, Small Interfering, pubmed-meshheading:16374848-Rats, pubmed-meshheading:16374848-Rats, Sprague-Dawley, pubmed-meshheading:16374848-Response Elements
pubmed:year
2006
pubmed:articleTitle
Nrf2 is increased by CYP2E1 in rodent liver and HepG2 cells and protects against oxidative stress caused by CYP2E1.
pubmed:affiliation
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural