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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1985-7-17
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pubmed:abstractText |
Previous studies have indicated that the presence of cytotoxic levels of menadione (2-methyl-1,4-naphthoquinone) causes rapid changes in intracellular thiol and Ca2+ homeostasis in isolated rat hepatocytes. The present investigation was undertaken to examine these effects in the intact liver. Rat livers were therefore perfused with Krebs-Henseleit buffer containing 1.3 mM Ca2+ using a single-pass mode, and the perfusate Ca2+ level was monitored with an on-line Ca2+-selective electrode. Infusion of menadione elicited an increased O2 uptake by the liver, followed by a dose-dependent decrease in the perfusate level of Ca2+. Hepatic accumulation of Ca2+ was accompanied by stimulation of cytosolic phosphorylase a activity. Cessation of menadione infusion resulted in gradual recovery of perfusate Ca2+ to base levels. Ca2+ uptake was not accompanied by decreases in reduced pyridine nucleotide or ATP levels in the liver as evidenced by measurements either during maximal Ca2+ uptake or after recovery. However, Ca2+ uptake was correlated with decreased glutathione and increased glutathione disulfide levels in the liver, both of which reversed during recovery from Ca2+ uptake. Moreover, depletion of hepatic glutathione by pretreatment with diethylmaleate resulted in increased Ca2+ uptake during menadione infusion. The amount of protein-bound mixed disulfides showed a particularly striking relationship to Ca2+ uptake, reaching a maximal level during Ca2+ uptake and reversing toward normal value during recovery from Ca2+ accumulation. The present findings suggest that menadione-induced Ca2+ uptake is due to plasma membrane dysfunction as a result of loss of protein thiol groups critical for maintaining the plasma membrane Ca2+ extrusion mechanism. Our model offers a particularly useful opportunity to study mechanisms underlying toxic disturbances in Ca2+ homeostasis in the intact liver, since Ca2+ fluxes can be monitored under conditions in which cellular control mechanisms are not obliterated by excessive toxicity.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Disulfides,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfhydryl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin K
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0014-2956
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
149
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
201-6
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pubmed:dateRevised |
2007-7-23
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pubmed:meshHeading |
pubmed-meshheading:3996400-Animals,
pubmed-meshheading:3996400-Calcium,
pubmed-meshheading:3996400-Disulfides,
pubmed-meshheading:3996400-Energy Metabolism,
pubmed-meshheading:3996400-Glutathione,
pubmed-meshheading:3996400-Liver,
pubmed-meshheading:3996400-Male,
pubmed-meshheading:3996400-Oxygen Consumption,
pubmed-meshheading:3996400-Perfusion,
pubmed-meshheading:3996400-Proteins,
pubmed-meshheading:3996400-Rats,
pubmed-meshheading:3996400-Rats, Inbred Strains,
pubmed-meshheading:3996400-Sulfhydryl Compounds,
pubmed-meshheading:3996400-Vitamin K
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pubmed:year |
1985
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pubmed:articleTitle |
Accumulation of Ca2+ induced by cytotoxic levels of menadione in the isolated, perfused rat liver.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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