Source:http://linkedlifedata.com/resource/pubmed/id/18255154
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| Predicate | Object |
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| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2008-3-17
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| pubmed:abstractText |
Cu-induced oxidative damage is associated with cancer, diabetes, neurodegenerative and age related diseases. The quest for Cu-chelators as potential antioxidants spans the past decades. Yet, biocompatible Cu-chelators that do not alter the normal metal-ion homeostasis are still lacking. Here, we explored the potential of natural and synthetic nucleotides and inorganic phosphates as inhibitors of the Cu(I)/(II)-induced ()OH formation via either the Fenton or Haber-Weiss mechanisms. For this purpose, we studied by ESR the modulation of Cu-induced ()OH production, from the decomposition of H(2)O(2), by nucleotides and phosphates. ATP inhibited both Cu(I) and Cu(II) catalyzed reactions (IC(50) 0.11 and 0.04mM, respectively). Likewise, adenosine 5'-beta,gamma-methylene triphosphate (AMP-PCP), adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S), ADP and tripolyphosphate were identified as good inhibitors. However, AMP and adenosine were poor inhibitors in the Cu(I)-H(2)O(2) system, IC(50) ca. 1.2mM, and radical enhancers in the Cu(II)-H(2)O(2) system. The best antioxidant was adenosine 5'-[beta,gamma-imino] triphosphate (AMP-PNP) (IC(50) 0.05mM at Cu(I)-H(2)O(2) system) which was 15 times more active than the known antioxidant Trolox. ATP and analogues inhibit Cu-induced ()OH formation through an ion chelation rather than a scavenging mechanism. Two phosphate groups are required for making active Fenton-reaction inhibitors. Nucleotides and phosphates triggered a biphasic modulation of the Haber-Weiss reaction, but a monophasic inhibition of the Fenton reaction. We conclude that nucleotides at sub mM concentrations can prevent Cu-induced OH radical formation from H(2)O(2), and hence may possibly prevent oxidative damage.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0162-0134
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
102
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
862-81
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| pubmed:meshHeading | |
| pubmed:year |
2008
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| pubmed:articleTitle |
Can nucleotides prevent Cu-induced oxidative damage?
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| pubmed:affiliation |
Department of Chemistry, Gonda-Goldschmied Medical Research Center, Bar-Ilan University, Ramat-Gan 52900, Israel.
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| pubmed:publicationType |
Journal Article
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