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Activity, regulation, copy number and function in the glyoxalase system
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Rabbani, Naila, Xue, Mingzhan and Thornalley, Paul J. (2014) Activity, regulation, copy number and function in the glyoxalase system. Biochemical Society Transactions, Volume 42 (Number 2). pp. 419-424. doi:10.1042/BST20140008
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Official URL: http://dx.doi.org/10.1042/BST20140008
Abstract
Molecular, catalytic and structural properties of glyoxalase pathway enzymes of many species are now known. Current research has focused on the regulation of activity and expression of Glo1 (glyoxalase I) and Glo2 (glyoxalase II) and their role in health and disease. Human GLO1 has MRE (metal-response element), IRE (insulin-response element), E2F4 (early gene 2 factor isoform 4), AP-2α (activating enhancer-binding protein 2α) and ARE (antioxidant response-element) regulatory elements and is a hotspot for copy number variation. The human Glo2 gene, HAGH (hydroxyacylglutathione hydrolase), has a regulatory p53-response element. Glo1 is linked to healthy aging, obesity, diabetes and diabetic complications, chronic renal disease, cardiovascular disease, other disorders and multidrug resistance in cancer chemotherapy. Mathematical modelling of the glyoxalase pathway predicts that pharmacological levels of increased Glo1 activity markedly decrease cellular methylglyoxal and related glycation, and pharmacological Glo1 inhibition markedly increases cellular methylglyoxal and related glycation. Glo1 inducers are in development to sustain healthy aging and for treatment of vascular complications of diabetes and other disorders, and cell-permeant Glo1 inhibitors are in development for treatment of multidrug-resistant tumours, malaria and potentially pathogenic bacteria and fungi.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Divisions: | Faculty of Medicine > Warwick Medical School > Health Sciences > Clinical Trials Unit Faculty of Medicine > Warwick Medical School > Health Sciences Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School |
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| Journal or Publication Title: | Biochemical Society Transactions | ||||
| Publisher: | Portland Press Ltd | ||||
| ISSN: | 0300-5127 | ||||
| Official Date: | April 2014 | ||||
| Dates: |
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| Volume: | Volume 42 | ||||
| Number: | Number 2 | ||||
| Page Range: | pp. 419-424 | ||||
| DOI: | 10.1042/BST20140008 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access |
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