Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-11-7
pubmed:abstractText
Recent studies have shown that exposure of LLC-PK1 cells to micromolar concentrations of Cd2+ for 1-4 hr causes the disruption of the junctions between the cells, whereas exposure to higher concentrations of Cd2+ for longer periods of time causes more severe toxic effects and cell death. Studies suggesting that glutathione may serve a protective role against Cd2+ toxicity in other tissues and cells led us to examine the effects of glutathione depletion on the cytotoxic actions of Cd2+ in the LLC-PK1 cell line. Confluent cells on Falcon cell culture inserts were depleted of glutathione by exposing them to 250 microM buthionine sulfoximine for 18 hr and then exposed to various concentrations of Cd2+ for up to 24 hr. The integrity of cell-cell junctions was assessed by morphologic observation of the cells and by monitoring the transepithelial electrical resistance. Cell viability was evaluated by monitoring the release of lactate dehydrogenase into the medium. The results showed that depleting the cells of glutathione did not alter the early junction-perturbing effects of Cd2+, but greatly enhanced the lethal effects. In both the glutathione-depleted and the normal cells, junctional changes were evident after as little as 1 hr of Cd2+ exposure. While the normal cells did not begin to die until they had been exposed to Cd2+ for 12-24 hr, the glutathione-depleted cells began to die after only 8 hr of Cd2+ exposure. Additional results showed that Cd2+ exposure had no effect on the total levels of glutathione at the time in which the junctional effects were occurring, but caused a marked decrease in glutathione levels at the time the cells were dying. These results indicate that the early junctional effects of Cd2+ do not result from alterations in intracellular glutathione or sulfhydryl metabolism, whereas the more severe cytotoxic effects and cell death may involve glutathione-sensitive mechanisms.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0041-008X
pubmed:author
pubmed:issnType
Print
pubmed:volume
134
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
285-95
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Effects of glutathione depletion on the cytotoxic actions of cadmium in LLC-PK1 cells.
pubmed:affiliation
Department of Pharmacology, Midwestern University, Downers Grove, Illinois 60515, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.