CYP2E1 Sensitizes the Liver to LPS- and TNF α-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases
Joint Authors
Wu, Defeng
Wang, Xiaodong
Yang, Lili
Cederbaum, Arthur I.
Source
International Journal of Hepatology
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-19, 19 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2011-10-18
Country of Publication
Egypt
No. of Pages
19
Main Subjects
Abstract EN
The mechanisms by which alcohol causes cell injury are not clear.
A major mechanism is the role of lipid peroxidation and oxidative stress in alcohol toxicity.
Many pathways have been suggested to play a role in how alcohol induces oxidative stress.
Considerable attention has been given to alcohol elevated production of lipopolysaccharide (LPS) and TNFα and to alcohol induction of CYP2E1.
These two pathways are not exclusive of each other; however, interactions between them, have not been extensively evaluated.
Increased oxidative stress from induction of CYP2E1 sensitizes hepatocytes to LPS and TNFα toxicity and oxidants, activation of inducible nitric oxide synthase and p38 and JNK MAP kinases, and mitochondrial dysfunction are downstream mediators of this CYP2E1-LPS/TNFα-potentiated hepatotoxicity.
This paper will summarize studies showing potentiated interactions between these two risk factors in promoting liver injury and the mechanisms involved including activation of the mitogen-activated kinase kinase kinase ASK-1.
Decreasing either cytosolic or mitochondrial thioredoxin in HepG2 cells expressing CYP2E1 causes loss of cell viability and elevated oxidative stress via an ASK-1/JNK-dependent mechanism.
We hypothesize that similar interactions occur as a result of ethanol induction of CYP2E1 and TNFα.
American Psychological Association (APA)
Cederbaum, Arthur I.& Yang, Lili& Wang, Xiaodong& Wu, Defeng. 2011. CYP2E1 Sensitizes the Liver to LPS- and TNF α-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases. International Journal of Hepatology،Vol. 2012, no. 2012, pp.1-19.
https://search.emarefa.net/detail/BIM-482629
Modern Language Association (MLA)
Cederbaum, Arthur I.…[et al.]. CYP2E1 Sensitizes the Liver to LPS- and TNF α-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases. International Journal of Hepatology No. 2012 (2012), pp.1-19.
https://search.emarefa.net/detail/BIM-482629
American Medical Association (AMA)
Cederbaum, Arthur I.& Yang, Lili& Wang, Xiaodong& Wu, Defeng. CYP2E1 Sensitizes the Liver to LPS- and TNF α-Induced Toxicity via Elevated Oxidative and Nitrosative Stress and Activation of ASK-1 and JNK Mitogen-Activated Kinases. International Journal of Hepatology. 2011. Vol. 2012, no. 2012, pp.1-19.
https://search.emarefa.net/detail/BIM-482629
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-482629