Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation
Biochemical Journal, Volume 443, No. 1, Year 2012
Notification
URL copied to clipboard!
Description
Abnormal cellular accumulation of the dicarbonyl metabolite MG (methylglyoxal) occurs on exposure to high glucose concentrations, inflammation, cell aging and senescence. It is associated with increased MG-adduct content of protein and DNA linked to increased DNA strand breaks and mutagenesis, mitochondrial dysfunction and ROS (reactive oxygen species) formation and cell detachment from the extracellular matrix. MG-mediated damage is countered by glutathione-dependent metabolism by Glo1 (glyoxalase 1). It is not known, however, whether Glo1 has stress-responsive up-regulation to counter periods of high MG concentration or dicarbonyl stress. We identified a functional ARE (antioxidant-response element) in the 5′-untranslated region of exon 1 of the mammalian Glo1 gene. Transcription factor Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2) binds to this ARE, increasing basal and inducible expression of Glo1. Activators of Nrf2 induced increased Glo1 mRNA, protein and activity. Increased expression of Glo1 decreased cellular and extracellular concentrations of MG, MG-derived protein adducts, mutagenesis and cell detachment. Hepatic, brain, heart, kidney and lung Glo1 mRNA and protein were decreased in Nrf2 -/- mice, and urinary excretion of MG protein and nucleotide adducts were increased approximately 2-fold. We conclude that dicarbonyl stress is countered by up-regulation of Glo1 in the Nrf2 stress-responsive system, protecting protein and DNA from increased damage and preserving cell function. © The Authors Journal compilation © 2012 Biochemical Society.
Authors & Co-Authors
Xue, Mingzhan
United Kingdom, Coventry
University of Warwick
Rabbani, Naila
United Kingdom, Coventry
University of Warwick
Momiji, Hiroshi
United Kingdom, Coventry
University of Warwick
Imbasi, Precious
United Kingdom, Colchester
University of Essex
Nigeria, Amassoma
Niger Delta University
Anwar, M. Maqsud
United Kingdom, Coventry
University of Warwick
Kitteringham, Neil
United Kingdom, Liverpool
University of Liverpool
Park, B. Kevin
United Kingdom, Liverpool
University of Liverpool
Souma, T.
Japan, Sendai
Graduate School of Medicine
Moriguchi, Takashi
Japan, Sendai
Graduate School of Medicine
Yamamoto, Masayuki
Japan, Sendai
Graduate School of Medicine
Thornalley., Paul J.
United Kingdom, Coventry
University of Warwick
United Kingdom, Colchester
University of Essex
Statistics
Citations: 244
Authors: 11
Affiliations: 5
Identifiers
Doi:
10.1042/BJ20111648
ISSN:
02646021
e-ISSN:
14708728
Research Areas
Cancer
Genetics And Genomics