Linked Life Data

16243847

Source:http://linkedlifedata.com/resource/pubmed/id/16243847

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2006-1-12
pubmed:abstractText
Metallothionein (MT) releases zinc under oxidative stress conditions in cultured cells. The change in the MT molecule after zinc release in vivo is unknown although in vitro studies have identified MT disulfide bond formation. The present study was undertaken to test the hypothesis that MT disulfide bond formation occurs in vivo. A cardiac-specific MT-overexpressing transgenic mouse model was used. Mice were administered saline as a control or doxorubicin (20 mg/kg), which is an effective anticancer drug but with severe cardiac toxicity at least partially because of the generation of reactive oxygen species. A differential alkylation of cysteine residues in MT of the heart extracts was performed. Free and metal-bound cysteines were first trapped by N-ethylmaleimide and the disulfide bonds were reduced by dithiothreitol followed by alkylation with radiolabeled iodoacetamide. Analyses of the differentially alkylated MTs in the heart extract by high performance liquid chromatography, SDS-PAGE, Western blot, and mass spectrometry revealed that disulfide bonds were present in MT in vivo under both physiological and oxidative stress conditions. More disulfide bonds were found in MT under the oxidative stress conditions. The MT disulfide bonds were likely intramolecular and both alpha- and beta-domains were involved in the disulfide bond formation, although the alpha-domain appeared to be more easily oxidized than the beta-domain. The results suggest that under physiological conditions, the formation of MT disulfide bonds is involved in the regulation of zinc homeostasis. Additional zinc release from MT under oxidative stress conditions is accompanied by more MT disulfide bond formation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
681-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16243847-Animals, pubmed-meshheading:16243847-Antineoplastic Agents, pubmed-meshheading:16243847-Blotting, Western, pubmed-meshheading:16243847-Chromatography, High Pressure Liquid, pubmed-meshheading:16243847-Cysteine, pubmed-meshheading:16243847-Disulfides, pubmed-meshheading:16243847-Dithiothreitol, pubmed-meshheading:16243847-Doxorubicin, pubmed-meshheading:16243847-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:16243847-Ethylmaleimide, pubmed-meshheading:16243847-Iodoacetamide, pubmed-meshheading:16243847-Mass Spectrometry, pubmed-meshheading:16243847-Metallothionein, pubmed-meshheading:16243847-Mice, pubmed-meshheading:16243847-Mice, Transgenic, pubmed-meshheading:16243847-Myocardium, pubmed-meshheading:16243847-Oxidative Stress, pubmed-meshheading:16243847-Peptides, pubmed-meshheading:16243847-Protein Structure, Tertiary, pubmed-meshheading:16243847-Spectrometry, Mass, Electrospray Ionization, pubmed-meshheading:16243847-Spectrometry, Mass, Matrix-Assisted Laser..., pubmed-meshheading:16243847-Time Factors, pubmed-meshheading:16243847-Trypsin, pubmed-meshheading:16243847-Zinc
pubmed:year
2006
pubmed:articleTitle
Metallothionein disulfides are present in metallothionein-overexpressing transgenic mouse heart and increase under conditions of oxidative stress.
pubmed:affiliation
Department of Medicine, University of Louisville, KY 40292, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural