Enhanced 4-Hydroxynonenal Resistance in KEAP1 Silenced Human Colon Cancer Cells
Joint Authors
Kwak, Mi-Kyoung
Jung, Kyeong-Ah
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-16, 16 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-05-22
Country of Publication
Egypt
No. of Pages
16
Main Subjects
Natural & Life Sciences (Multidisciplinary)
Biology
Abstract EN
Nuclear factor erythroid 2-related factor 2 (NRF2) is the transcription factor that regulates an array of antioxidant/detoxifying genes for cellular defense.
The conformational changes of Kelch-like ECH-associated protein 1 (KEAP1), a cytosolic repressor protein of NRF2, by various stimuli result in NRF2 liberation and accumulation in the nucleus.
In the present study, we aimed to investigate the effect of KEAP1 knockdown on NRF2 target gene expression and its toxicological implication using human colon cancer cells.
The stable KEAP1-knockdown HT29 cells exhibit elevated levels of NRF2 and its target gene expressions.
In particular, the mRNA levels of aldo-keto reductases (AKR1C1, 1C2, 1C3, 1B1, and 1B10) were substantially increased in KEAP1 silenced HT29 cells.
These differential AKRs expressions appear to contribute to protection against oxidative stress.
The KEAP1-knockdown cells were relatively more resistant to hydrogen peroxide (H2O2) and 4-hydroxynonenal (4HNE) compared to the control cells.
Accordantly, we observed accumulation of 4HNE protein adducts in H2O2- or 4HNE-treated control cells, whereas KEAP1-knockdown cells did not increase adduct formation.
The treatment of KEAP1-silenced cells with AKR1C inhibitor flufenamic acid increased 4HNE-induced cellular toxicity and protein adduct formation.
Taken together, these results indicate that AKRs, which are NRF2-dependent highly inducible gene clusters, play a role in NRF2-mediated cytoprotection against lipid peroxide toxicity.
American Psychological Association (APA)
Jung, Kyeong-Ah& Kwak, Mi-Kyoung. 2013. Enhanced 4-Hydroxynonenal Resistance in KEAP1 Silenced Human Colon Cancer Cells. Oxidative Medicine and Cellular Longevity،Vol. 2013, no. 2013, pp.1-16.
https://search.emarefa.net/detail/BIM-471055
Modern Language Association (MLA)
Jung, Kyeong-Ah& Kwak, Mi-Kyoung. Enhanced 4-Hydroxynonenal Resistance in KEAP1 Silenced Human Colon Cancer Cells. Oxidative Medicine and Cellular Longevity No. 2013 (2013), pp.1-16.
https://search.emarefa.net/detail/BIM-471055
American Medical Association (AMA)
Jung, Kyeong-Ah& Kwak, Mi-Kyoung. Enhanced 4-Hydroxynonenal Resistance in KEAP1 Silenced Human Colon Cancer Cells. Oxidative Medicine and Cellular Longevity. 2013. Vol. 2013, no. 2013, pp.1-16.
https://search.emarefa.net/detail/BIM-471055
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-471055