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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
3
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pubmed:dateCreated |
1997-11-14
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pubmed:abstractText |
This investigation tested the hypothesis that depletion of intracellular glutathione, in contrast to its oxidation could lead to non-native oxidation of protein thiols, thereby trapping proteins in an unstable conformation. Chinese hamster cells were exposed to the alpha, beta-unsaturated dicarboxylic acid diethylmaleate in order to produce rapid glutathione (GSH) depletion without oxidation. Measurement of the fluorescence of oxidized 2',7'-dichlorofluorescein diacetate indicated that reactive oxygen species accumulated in GSH depleted cells. Glutathione depletion was found to alter protein thiol/disulfide exchange ratios such that 17 to 23 nmol of protein SH/mg protein underwent oxidation. Differential scanning calorimetry (DSC) of glutathione depleted cells yielded a profile of specific heat capacity versus temperature that was characteristic of cells containing destabilized and denatured protein. In addition, cells depleted of glutathione exhibited a two-fold increase in NP-40 insoluble protein. These results indicate that depletion of intracellular glutathione caused oxidation of protein thiols, protein denaturation and aggregation and provide a mechanism to explain how GSH depletion can initiate stress responses.
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pubmed:grant | |
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 |
Sep
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pubmed:issn |
1355-8145
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
2
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
191-8
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pubmed:dateRevised |
2008-11-20
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pubmed:meshHeading |
pubmed-meshheading:9314607-Animals,
pubmed-meshheading:9314607-CHO Cells,
pubmed-meshheading:9314607-Cricetinae,
pubmed-meshheading:9314607-Glutathione,
pubmed-meshheading:9314607-Intracellular Fluid,
pubmed-meshheading:9314607-Oxidation-Reduction,
pubmed-meshheading:9314607-Protein Denaturation,
pubmed-meshheading:9314607-Proteins,
pubmed-meshheading:9314607-Reactive Oxygen Species,
pubmed-meshheading:9314607-Sulfhydryl Compounds
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pubmed:year |
1997
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pubmed:articleTitle |
Destabilization and denaturation of cellular protein by glutathione depletion.
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pubmed:affiliation |
Vanderbilt Center for Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Freemaml@ctrvax.vanderbilt.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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