Linked Life Data

15603755

Source:http://linkedlifedata.com/resource/pubmed/id/15603755

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2004-12-17
pubmed:abstractText
Cytochromes P450 are responsible for metabolism of most xenobiotics and are required for the efficient elimination of foreign chemicals from the body. Paradoxically, these enzymes also metabolically activate biologically inert compounds to electrophilic derivatives that can cause toxicity, cell death and sometimes cellular transformation resulting in cancer. To establish the role of these enzymes in toxicity and carcinogenicity in vivo, gene knockout mice have been developed. To illustrate the role of P450s in toxicity, CYP2E1-null mice were employed with the commonly used analgesic drug acetaminophen. CYP2E1 is the rate-limiting enzyme that initiates the cascade of events leading to acetaminophen hepatotoxicity; in the absence of this P450, toxicity will only be apparent at high concentrations. Other enzymes and nuclear receptors are also involved in activation or inactivating chemicals. CYP2E1 is induced by alcohol and the primary P450 that carries out ethanol oxidation that can lead to the production of activated oxygen species and oxidative stress that elevate ERK1/2 phosphorylation through EGRF/c-Raf signaling. Paradoxically, activation of this pathway inhibits apoptotic cell death stimulated by reactive oxygen generating chemicals but accelerates necrotic cell death produced by polyunsaturated fatty acids. CYP2E1 is thought to contribute to liver pathologies that result from alcoholic liver disease and non-alcoholic steatohepatitis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0027-5107
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
569
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
101-10
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2005
pubmed:articleTitle
Role of cytochromes P450 in chemical toxicity and oxidative stress: studies with CYP2E1.
pubmed:affiliation
Laboratory of Metabolism, National Cancer Institute, Bethesda, MD 20892, USA. fjgonz@helix.nih.gov
pubmed:publicationType
Journal Article, Review