Linked Life Data

12730608

Source:http://linkedlifedata.com/resource/pubmed/id/12730608

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-6-18
pubmed:abstractText
Reduction of the pentavalent arsenate (AsV) to the thiol-reactive arsenite (AsIII) toxifies this environmentally prevalent form of arsenic, yet its biochemical mechanism in mammals is incompletely understood. Purine nucleoside phosphorylase (PNP) has been shown recently to function as an AsV reductase in vitro, provided its substrate (inosine or guanosine) and an appropriate dithiol (e.g., dithiothreitol, DTT) were present. It was of interest to know if this ubiquitous enzyme played a significant role in reduction of AsV to AsIII in vivo. Two approaches were used to test this. First, it was determined if compounds that influenced AsV reduction by purified PNP (i.e., nucleosides, thiols, and PNP inhibitors) would similarly affect reduction of AsV by human erythrocytes. Erythrocytes were incubated with AsV, and the formed AsIII was quantified by HPLC-hydride generation-atomic fluorescence spectrometry. The red blood cells reduced AsV at a considerable rate, which could be enhanced by inosine or inosine plus DTT. These stimulated AsIII formation rates were PNP-dependent, as PNP inhibitors strongly inhibited them. In contrast, PNP inhibitors had little if any inhibitory effect on AsIII formation in the absence of exogenous inosine, indicating that this basal rate of AsV reduction is PNP-independent. Second, the role of PNP in reduction of AsV in vivo was also assessed by investigating the effect of the PNP inhibitor BCX-1777 on the biotransformation of AsV in control and DTT-treated rats with cannulated bile duct and ligated renal pedicles. Although it abolished hepatic PNP activity, BCX-1777 influenced neither the biliary excretion of AsIII and monomethylarsonous acid, nor the tissue concentration of AsV and its metabolites in either group of AsV-injected rats. Thus, despite its in vitro activity, PNP does not appear to play a significant role in AsV reduction in human erythrocytes and in rats in vivo. Further research should clarify the in vivo relevant mechanisms of AsV reduction in mammals.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
74
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22-31
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed-meshheading:12730608-Animals, pubmed-meshheading:12730608-Anticarcinogenic Agents, pubmed-meshheading:12730608-Blotting, Western, pubmed-meshheading:12730608-Body Weight, pubmed-meshheading:12730608-Bone Density, pubmed-meshheading:12730608-Calcitriol, pubmed-meshheading:12730608-Colon, pubmed-meshheading:12730608-Cytochrome P-450 Enzyme System, pubmed-meshheading:12730608-Diet, pubmed-meshheading:12730608-Eating, pubmed-meshheading:12730608-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:12730608-Female, pubmed-meshheading:12730608-Indoles, pubmed-meshheading:12730608-Liver, pubmed-meshheading:12730608-Male, pubmed-meshheading:12730608-Microsomes, Liver, pubmed-meshheading:12730608-Organ Size, pubmed-meshheading:12730608-Rats, pubmed-meshheading:12730608-Rats, Sprague-Dawley, pubmed-meshheading:12730608-Sex Characteristics, pubmed-meshheading:12730608-Testosterone
pubmed:year
2003
pubmed:articleTitle
Arsenate reduction in human erythrocytes and rats--testing the role of purine nucleoside phosphorylase.
pubmed:affiliation
Department of Pharmacology and Pharmacotherapy, University of Pécs, Medical School, Szigeti út 12, H-7624 Pécs, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't