Linked Life Data

11594736

Source:http://linkedlifedata.com/resource/pubmed/id/11594736

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-10-11
pubmed:abstractText
Reactive intermediates derived from nitric oxide ((*)NO) are thought to play a contributing role in disease states associated with inflammation and infection. We show here that glutathione S-transferases (GSTs), principal enzymes responsible for detoxification of endogenous and exogenous electrophiles, are susceptible to inactivation by reactive nitrogen species (RNS). Treatment of isolated GSTs or rat liver homogenates with either peroxynitrite, the myeloperoxidase/hydrogen peroxide/nitrite system, or tetranitromethane, resulted in loss of GST activity with a concomitant increase in the formation of protein-associated 3-nitrotyrosine (NO(2)Tyr). This inactivation was only partially (<25%) reversible by dithiothreitol, and exposure of GSTs to hydrogen peroxide or S-nitrosoglutathione was only partially inhibitory (<25%) and did not result in protein nitration. Thus, irreversible modifications such as tyrosine nitration may have contributed to GST inactivation by RNS. Since all GSTs contain a critical, highly conserved, active-site tyrosine residue, we postulated that this Tyr residue might present a primary target for nitration by RNS, thus leading to enzyme inactivation. To directly investigate this possibility, we analyzed purified mouse liver GST-mu, following nitration by several RNS, by trypsin digestion, HPLC separation, and matrix-assisted laser desorption/ionization-time of flight analysis, to determine the degree of tyrosine nitration of individual Tyr residues. Indeed, nitration was found to occur preferentially on several tyrosine residues located in and around the GST active site. However, RNS concentrations that resulted in near complete GST inactivation only caused up to 25% nitration of even preferentially targeted tyrosine residues. Hence, nitration of active-site tyrosine residues may contribute to GST inactivation by RNS, but is unlikely to fully account for enzyme inactivation. Overall, our studies illustrate a potential mechanism by which RNS may promote (oxidative) injury by environmental pollutants in association with inflammation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0003-9861
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
394
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
216-28
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11594736-Animals, pubmed-meshheading:11594736-Chromatography, Affinity, pubmed-meshheading:11594736-Chromatography, High Pressure Liquid, pubmed-meshheading:11594736-Dose-Response Relationship, Drug, pubmed-meshheading:11594736-Glutathione Transferase, pubmed-meshheading:11594736-Hydrogen Peroxide, pubmed-meshheading:11594736-Liver, pubmed-meshheading:11594736-Male, pubmed-meshheading:11594736-Mice, pubmed-meshheading:11594736-Nitrates, pubmed-meshheading:11594736-Nitric Oxide, pubmed-meshheading:11594736-Oxidants, pubmed-meshheading:11594736-Peptide Fragments, pubmed-meshheading:11594736-Peroxynitrous Acid, pubmed-meshheading:11594736-Rats, pubmed-meshheading:11594736-Rats, Sprague-Dawley, pubmed-meshheading:11594736-Reducing Agents, pubmed-meshheading:11594736-S-Nitrosoglutathione, pubmed-meshheading:11594736-Spectrometry, Mass, Matrix-Assisted Laser..., pubmed-meshheading:11594736-Tyrosine
pubmed:year
2001
pubmed:articleTitle
Inactivation of glutathione S-transferases by nitric oxide-derived oxidants: exploring a role for tyrosine nitration.
pubmed:affiliation
Center for Comparative Respiratory Biology and Medicine, University of California, Davis, California 95616, USA. patwong@ucdavis.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't