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Nrf2-keap1 signaling as a potential target for chemoprevention of inflammation-associated carcinogenesis

Cited 120 time in Web of Science Cited 124 time in Scopus
Authors
Kundu, Joydeb Kumar; Surh, Young-Joon
Issue Date
2010-06
Citation
Pharmaceutical Research, Vol.27 No.6, pp.999-1013
Keywords
anti-inflammationchemopreventionchemopreventive agentsinflammationKeap1Nrf2redox signaling
Abstract
Persistent inflammatory tissue damage is causally associated with each stage of carcinogenesis. Inflammation-induced generation of reactive oxygen species, reactive nitrogen species, and other reactive species not only cause DNA damage and subsequently mutations, but also stimulate proliferation of initiated cells and even metastasis and angiogenesis. Induction of cellular cytoprotective enzymes (e.g., heme oxygenase-1, NAD(P)H:quinone oxidoreductase, superoxide dismutase, glutathione-S-transferase, etc.) has been shown to mitigate aforementioned events implicated in inflammation-induced carcinogenesis. A unique feature of genes encoding these cytoprotective enzymes is the presence of a cis-acting element, known as antioxidant response element (ARE) or electrophile response element (EpRE), in their promoter region. A stress-responsive transcription factor, nuclear factor erythroid-2-related factor-2 (Nrf2), initially recognized as a key transcriptional regulator of various cytoprotective enzymes, is known to play a pivotal role in cellular defense against inflammatory injuries. Activation of Nrf2 involves its release from the cytosolic repressor Kelch-like ECH-associated protein-1 (Keap1) and subsequent stabilization and nuclear localization for ARE/EpRE binding. Genetic or pharmacologic inactivation of Nrf2 has been shown to abolish cytoprotective capability and to aggravate experimentally induced inflammatory injuries. Thus, Nrf2-mediated cytoprotective gene induction is an effective strategy for the chemoprevention of inflammation-associated carcinogenesis.
ISSN
0724-8741
URI
https://hdl.handle.net/10371/172885
DOI
https://doi.org/10.1007/s11095-010-0096-8
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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