| Identification and characterization of an Nrf2-mediated ARE upstream of the rat glutamate cysteine ligase catalytic subunit gene (GCLC). | |
| | |
MedLine Citation:
|
PMID: 19459163 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
The antioxidant response element (ARE) is an essential component of upstream regulatory sequences present on genes for most phase II detoxification enzymes, including the glutamate cysteine ligase catalytic subunit (GCLC). NF-E2-related factor 2 (Nrf2) is a principal transcription factor that binds to the ARE and plays a key role in cellular responses to stress via the Keap1-Nrf2-ARE pathway. However, the ARE that mediates human GCLC gene expression has not been found in the rat. Thus, how the ARE-mediated Keap1-Nrf2-ARE pathway regulates glutathione homeostasis in the rat remains a puzzle. We have identified a putative ARE sequence approximately 4 kb upstream in the rat GCLC. We further defined the rat GCLC-ARE in the category with the most ARE characters, that is, this rat GCLC-ARE is a sequence-specific site that significantly enhances promoter activity in reporter genes. The rat GCLC-ARE is an Nrf2-mediated element to which binding has been demonstrated in nuclear extracts and induced by tert-butylhydroquinone. Given the central role that rat models play in toxicology and pathology, this first discovery of the rat GCLC-ARE enhancer similar to that found in the human gene has broad implications for the study of antioxidant defenses and their regulation in a number of different fields. |
| | |
Authors:
|
Muyao Li; Jen-Fu Chiu; Anne Kelsen; Shelly C Lu; Naomi K Fukagawa |
Related Documents
:
|
3752923 - Subcellular distribution of selenium in the liver from rats fed selenium from fish: sel... 3653273 - Effect of light history on retinal antioxidants and light damage susceptibility in the ... 1534053 - A comparison of intraperitoneal prostheses for the repair of abdominal muscular wall de... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
|
Title: Journal of cellular biochemistry Volume: 107 ISSN: 1097-4644 ISO Abbreviation: J. Cell. Biochem. Publication Date: 2009 Aug |
Date Detail:
|
Created Date: 2009-07-22 Completed Date: 2009-10-13 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8205768 Medline TA: J Cell Biochem Country: United States |
Other Details:
|
Languages: eng Pagination: 944-54 Citation Subset: IM |
Copyright Information:
|
(c) 2009 Wiley-Liss, Inc. |
Affiliation:
|
Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont 05405, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Base Sequence Catalytic Domain / genetics* Chromatin Immunoprecipitation Genes, Reporter Glutamate-Cysteine Ligase / genetics* Hydroquinones / pharmacology Luciferases / metabolism Molecular Sequence Data NF-E2-Related Factor 2 / metabolism* Nuclear Proteins / metabolism Protein Binding / drug effects Rats Rats, Inbred F344 Response Elements / genetics* |
| Grant Support | |
ID/Acronym/Agency:
|
AG00947/AG/NIA NIH HHS; AG21106/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Hydroquinones; 0/NF-E2-Related Factor 2; 0/Nfe2l2 protein, rat; 0/Nuclear Proteins; 1948-33-0/2-tert-butylhydroquinone; EC 1.13.12.-/Luciferases; EC 6.3.2.2/Glutamate-Cysteine Ligase; EC 6.3.2.2./GCLC protein, rat |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Reactive oxygen species-induced cell death of rat primary astrocytes through mitochondria-mediated m...
Next Document: Histone deacetylase inhibitors: Potential in cancer therapy.