Document Detail


Nitric oxide inactivates glyoxalase I in cooperation with glutathione.
MedLine Citation:
PMID:  11011147     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We previously found that glyoxalase I (Glo I) is inactivated upon exposure of human endothelial cells to extracellular nitric oxide (NO), and this event correlates with an increase in its pI on two-dimensional gels. In this study, we demonstrate that NO can modulate Glo I activity in cooperation with cellular glutathione (GSH). Severe depletion of intracellular GSH prevents the inactivation of Glo I in response to NO, although such depletion enhances the inactivation of glyceraldehyde-3-phosphate dehydrogenase (G3PDH), a well-known enzyme susceptible to NO-induced oxidation. S-Nitrosoglutathione (GSNO), an adduct of GSH and NO, lowers the activity of purified human Glo I, while S-nitrosocysteine (CysNO) inactivates the enzyme only in the presence of GSH. This indicates that a dysfunction in Glo I would require the formation of GSNO in situ. Competitive inhibitors of Glo I, S-(4-bromobenzyl)glutathione and its membrane-permeating form, completely abolish the NO action in vitro and inside cells, respectively. Taken together, these results reveal that Glo I can interact directly with GSNO, and that the interaction converts Glo I into an inactive form. Moreover, the data suggest that the substrate recognition site of Glo I might be involved in the interaction with GSNO.
Authors:
A Mitsumoto; K R Kim; G Oshima; M Kunimoto; K Okawa; A Iwamatsu; Y Nakagawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of biochemistry     Volume:  128     ISSN:  0021-924X     ISO Abbreviation:  J. Biochem.     Publication Date:  2000 Oct 
Date Detail:
Created Date:  2000-12-22     Completed Date:  2000-12-22     Revised Date:  2007-12-19    
Medline Journal Info:
Nlm Unique ID:  0376600     Medline TA:  J Biochem     Country:  JAPAN    
Other Details:
Languages:  eng     Pagination:  647-54     Citation Subset:  IM    
Affiliation:
School of Pharmaceutical Sciences, Kitasato University, Tokyo, 108-8641, Japan.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Cell Membrane Permeability
Cysteine / analogs & derivatives,  pharmacology
Electrophoresis, Gel, Two-Dimensional
Endothelium / cytology,  drug effects,  enzymology,  metabolism
Erythrocytes / enzymology
Glutathione / analogs & derivatives,  metabolism,  pharmacology*
Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors,  metabolism
Humans
Kinetics
Lactoylglutathione Lyase / antagonists & inhibitors*,  metabolism
Nitric Oxide / metabolism,  pharmacology*
Nitroso Compounds / pharmacology
S-Nitrosoglutathione
S-Nitrosothiols*
Chemical
Reg. No./Substance:
0/Nitroso Compounds; 0/S-Nitrosothiols; 10102-43-9/Nitric Oxide; 31702-37-1/S-(4-bromobenzyl)glutathione; 51209-75-7/S-nitrosocysteine; 52-90-4/Cysteine; 57564-91-7/S-Nitrosoglutathione; 70-18-8/Glutathione; EC 1.2.1.-/Glyceraldehyde-3-Phosphate Dehydrogenases; EC 4.4.1.5/Lactoylglutathione Lyase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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