Linked Life Data

12464267

Source:http://linkedlifedata.com/resource/pubmed/id/12464267

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-12-4
pubmed:abstractText
CYP2E1-dependent mitochondrial damage, in the presence or absence of extracellular calcium, was investigated. HepG2 cells expressing CYP2E1 (E47 cells) were preloaded with arachidonic acid (AA), washed, and incubated with iron-nitrilotriacetate 1:3 complex (Fe-NTA) in minimum essential medium (MEM) (1.8mM Ca(2+)) or Ca(2+)-free MEM (SMEM). Toxicity in SMEM was CYP2E1-dependent, necrotic, and lipid peroxidation-dependent. Intracellular calcium did not significantly change during the incubation in SMEM. Mitochondrial damage preceded the loss of plasma membrane integrity and was significant at 12h of incubation, in coincidence with the toxicity. E47 cells treated with AA+Fe in MEM also showed a decline of mitochondrial membrane potential (Delta(Psi)(m)) that preceded the loss of plasma membrane integrity, but starting at earlier times, e.g., 3h than in SMEM. The decline in Delta(Psi)(m) and the toxicity in both MEM and SMEM were inhibited by alpha-tocopherol and cyclosporin A, while the calpain inhibitor calpeptin was only effective in MEM. In conclusion, oxidative damage to mitochondria and the permeability transition plays a role in the CYP2E1-dependent toxicity of Fe+AA in HepG2 cells, both in MEM and SMEM. Ca(2+) mobilization and activation of calpain contributes to the more rapid onset of mitochondrial damage in MEM, while oxidative damage and lipid peroxidation are involved in the Ca(2+)-independent later onset of mitochondrial damage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0003-9861
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
408
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
162-70
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:12464267-Arachidonic Acid, pubmed-meshheading:12464267-Calcium, pubmed-meshheading:12464267-Calpain, pubmed-meshheading:12464267-Carcinoma, Hepatocellular, pubmed-meshheading:12464267-Culture Media, pubmed-meshheading:12464267-Cyclosporine, pubmed-meshheading:12464267-Cysteine Proteinase Inhibitors, pubmed-meshheading:12464267-Cytochrome P-450 CYP2E1, pubmed-meshheading:12464267-Cytosol, pubmed-meshheading:12464267-Dipeptides, pubmed-meshheading:12464267-Humans, pubmed-meshheading:12464267-Intracellular Membranes, pubmed-meshheading:12464267-Iron, pubmed-meshheading:12464267-Lipid Peroxidation, pubmed-meshheading:12464267-Liver Neoplasms, pubmed-meshheading:12464267-Mitochondria, Liver, pubmed-meshheading:12464267-Oxidative Stress, pubmed-meshheading:12464267-Permeability, pubmed-meshheading:12464267-Tumor Cells, Cultured, pubmed-meshheading:12464267-alpha-Tocopherol
pubmed:year
2002
pubmed:articleTitle
Ca2+-dependent and independent mitochondrial damage in HepG2 cells that overexpress CYP2E1.
pubmed:affiliation
Department of Pharmacology and Biological Chemistry, Mount Sinai School of Medicine, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.