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PMID: 10535991 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Nrf2 is essential for protection against acute pulmonary injury in mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 96 ·No. 22 ·1999-10-26 ·Pages 12731-6

Chan K, Kan YW

Abstract

Nrf2 is a member of the "cap 'n' collar" family of transcription factors. These transcription factors bind to the NF-E2 binding sites (GCTGAGTCA) that are essential for the regulation of erythroid-specific genes. Nrf2 is expressed in a wide range of tissues, many of which are sites of expression for phase 2 detoxification genes. Nrf2(-/-) mice are viable and have a normal phenotype under normal laboratory conditions. The NF-E2 binding site is a subset of the antioxidant response elements that have the sequence GCNNNGTCA. The antioxidant response elements are regulatory sequences found on promoters of several phase 2 detoxification genes that are inducible by xenobiotics and antioxidants. We report here that Nrf2(-/-) mice are extremely susceptible to the administration of the antioxidant butylated hydroxytoluene. With doses of butylated hydroxytoluene that are tolerated by wild-type mice, the Nrf2(-/-) mice succumb from acute respiratory distress syndrome. Gene expression studies show that the expression of several detoxification enzymes is altered in the Nrf2(-/-) mice. The Nrf2(-/-) mice may prove to be a good in vivo model for toxicological studies. As oxidative damage causes DNA breakage, these mice may also be useful for testing carcinogenic agents.

MeSH Terms
Animals Base Sequence Butylated Hydroxytoluene/toxicity DNA Primers DNA-Binding Proteins/genetics,physiology Lethal Dose 50 Lung Diseases/chemically induced,prevention & control Mice Mice, Inbred C57BL Mice, Knockout NF-E2-Related Factor 2 RNA, Messenger/genetics Trans-Activators/genetics,physiology
Chemicals
DNA Primers DNA-Binding Proteins NF-E2-Related Factor 2 Nfe2l2 protein, mouse RNA, Messenger Trans-Activators Butylated Hydroxytoluene
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Chan K
Cardiovascular Research Institute, University of California, San Francisco, CA 94143-0793, USA. ywkan.pangloss.ucsf.edu
Kan Y W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.96.22.12731
Published
1999-10-26
Pages
12731-6
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23072
Subset
IM
Grants
NIDDK NIH HHS · R01 DK016666 · United States
NIDDK NIH HHS · R37 DK016666 · United States
NIDDK NIH HHS · DK16666 · United States
NIDDK NIH HHS · DK502670 · United States
External Links
PubMed source DOI: 10.1073/pnas.96.22.12731 PMC Full Text View journal details
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