Linked Life Data

12566070

Source:http://linkedlifedata.com/resource/pubmed/id/12566070

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-2-4
pubmed:abstractText
Zinc has been shown to have antioxidant actions, which may be due, in part, to induction of metallothionein (MT). Such induction can protect tissues against various forms of oxidative injury because MT can function as an antioxidant. The objective of this study was to investigate if zinc or MT induction by zinc could afford protection against CYP2E1-dependent toxicity. HepG2 cells overexpressing CYP2E1 (E47cells) were treated with 60 microM arachidonic acid (AA), which is known to be toxic to these cells by a mechanism dependent on CYP2E1, oxidative stress, and lipid peroxidation. E47 cells were preincubated overnight in the absence or presence of metals such as zinc or cadmium that can induce MT. The culture medium containing the metals was removed, AA was added, and cell viability determined after 24 h incubation. Preincubation overnight with 150 microM zinc sulfate or 5 microM cadmium chloride induced a 20- to 30-fold increase of MT2A mRNA; high levels of MT2A mRNA were maintained during the subsequent challenge period with AA, even after the zinc was removed. MT protein levels were increased about 4- to 5-fold during the overnight preincubation with zinc and a 20- to 30-fold increase was observed 24 h after zinc removal during the AA challenge. The treatment with zinc was associated with significant protection against the loss of cell viability caused by AA in E47 cells. The zinc pretreatment protected about 50% against the DNA fragmentation, cell necrosis, the enhanced lipid peroxidation and increased generation of reactive oxygen species, and the loss of mitochondrial membrane potential induced by AA treatment in E47 cells. CYP2E1 catalytic activity and components of the cell antioxidant defense system such as glutathione (GSH), glutathione-S-transferase (GST), glutathione peroxidase (GPX), catalase, Cu,Zn superoxide dismutase (SOD), and MnSOD were not altered under these conditions. Zinc preincubation also protected the E47 cells against BSO-dependent toxicity. When E47 cells were coincubated with zinc plus AA for 24 h (i.e., zinc was not removed, nor was there a preincubation period prior to challenge with AA), AA toxicity was increased. Thus, zinc had a direct pro-oxidant effect in this model and an indirect antioxidant effect, perhaps via induction of MT. MT may have potential clinical utility for the prevention or improvement of liver injury produced by agents known to be metabolized by CYP2E1 to reactive intermediates and to cause oxidative stress.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0891-5849
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
34
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
443-55
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Metallothionein 2A induction by zinc protects HEPG2 cells against CYP2E1-dependent toxicity.
pubmed:affiliation
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.