Linked Life Data

12060676

Source:http://linkedlifedata.com/resource/pubmed/id/12060676

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2002-8-2
pubmed:abstractText
Bcl-2, a protein that blocks apoptosis by inhibiting the mitochondrial permeability transition (MPT) and release of cytochrome c appears to affect normal mitochondrial function by altering electron flow and increasing rates of reactive oxygen species (ROS) production. In this study, we show that glutathione (GSH) depletion induces ROS production and selective toxicity in HL60 cells that overexpress Bcl-2 compared with neomycin vector control cells. Toxicity was mediated by the MPT because it was blocked with the adenine nucleotide translocator (ANT) ligand bongkrekic acid and resulted in mitochondrial cytochrome c release, caspase 3 activation, and DNA fragmentation, indicating the involvement of an apoptotic pathway. Respiratory chain inhibitors stigmatellin and antimycin A, which inhibit Qo and Qi sites of respiratory chain complex III, respectively, blocked ROS production, preserved the redox state of protein thiols, and prevented cell death. These results indicate that in the absence of GSH, endogenous ROS generated at respiratory complex III induce MPT independently of Bcl-2. The results also suggest a new model for MPT in which the central pore protein ANT is regulated by adenine nucleotide and the activity of mitochondrial respiratory complex III.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1263-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Glutathione depletion enforces the mitochondrial permeability transition and causes cell death in Bcl-2 overexpressing HL60 cells.
pubmed:affiliation
Department of Biochemistry, Emory University School of Medicine, Atlanta, Georgia 30322-3050, USA. jeff30322@lycos.com
pubmed:publicationType
Journal Article