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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1998-10-13
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pubmed:abstractText |
Mono-thiols can act either as pro- or anti-oxidants during metal-catalyzed low density lipoprotein (LDL) peroxidation, however investigation of the role of vicinal thiols has been neglected. Therefore dihydrolipoic acid (DHLA), a vicinal dithiol, and lipoic acid, its oxidized form, were used to investigate Cu2+-mediated LDL peroxidation. We demonstrate here that DHLA inhibited Cu2+-dependent LDL peroxidation by chelating copper. DHLA (0-20 microM) increased lag-times of conjugated diene formation in LDL (100 microg/ml) oxidized with 5 microM Cu2+ in a concentration dependent manner, and this effect was saturated after 5 microM DHLA; enough to chelate all of the added Cu2+. In a similar fashion DHLA prevented LDL-mediated reduction of Cu2+ to Cu+. Lipoic acid had no effect in these systems. DHLA alone also reduced Cu2+, however this was inhibited when DHLA was in excess of the copper concentration. Hence there is complex formation between the two species. Copper:DHLA complex formation was further investigated and found to be dependent upon pH and the presence of oxygen. At low pH (<6), or in the absence of oxygen, the complex is stable, presumably due to vicinal thiol chelation. As the pH is increased, the carboxylate group also participates in copper chelation, this results in a less stable complex which is susceptible to oxidation, and copper is eventually released. Electron spin resonance studies demonstrate the formation of hydroxyl, but not superoxide, radicals during Cu2+-catalyzed DHLA oxidation. Thus in our LDL experiments at physiological pH, DHLA is able to either reductively inactivate Cu2+ when Cu2+ is in excess, or effectively chelate Cu2+ when DHLA is in excess. The Cu2+:DHLA complex eventually undergoes copper-catalyzed oxidation, copper is released and LDL peroxidation proceeds. DHLA, thus, has both pro- and antioxidant properties depending upon the ratio of Cu2+:DHLA and the pH. These results provide an additional mechanism of thiol-mediated formation of radicals and metal chelation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Chelating Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Copper,
http://linkedlifedata.com/resource/pubmed/chemical/Free Radicals,
http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Thioctic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/dihydrolipoic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0891-5849
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
287-97
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9680174-Chelating Agents,
pubmed-meshheading:9680174-Copper,
pubmed-meshheading:9680174-Electron Spin Resonance Spectroscopy,
pubmed-meshheading:9680174-Free Radicals,
pubmed-meshheading:9680174-Humans,
pubmed-meshheading:9680174-Hydrogen-Ion Concentration,
pubmed-meshheading:9680174-Kinetics,
pubmed-meshheading:9680174-Lipid Peroxidation,
pubmed-meshheading:9680174-Lipoproteins, LDL,
pubmed-meshheading:9680174-Oxidation-Reduction,
pubmed-meshheading:9680174-Sulfhydryl Compounds,
pubmed-meshheading:9680174-Thioctic Acid
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pubmed:year |
1998
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pubmed:articleTitle |
Thiol chelation of Cu2+ by dihydrolipoic acid prevents human low density lipoprotein peroxidation.
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pubmed:affiliation |
Department of Molecular and Cell Biology, University of California at Berkeley, 94720-3200, USA. johnkl@socrates.berkeley.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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