Linked Life Data

19418225

Source:http://linkedlifedata.com/resource/pubmed/id/19418225

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-5-18
pubmed:abstractText
It has been proposed that continuously generated hydrogen peroxide (H(2)O(2)) inhibits typical apoptosis and instead initiates an alternate, apoptosis-inducing factor (AIF)-dependent process. Aside from the role of AIF, however, the detailed morphological characterization of H(2)O(2)-induced cell death is not complete. This study examined the cellular mechanism(s) by which the continuous presence of H(2)O(2) induces cell death. We also further analyzed the precise role of AIF by inhibiting its expression with siRNA. Exposure of cells to H(2)O(2) generated by glucose oxidase caused mitochondrion-mediated, caspase-independent cell death. In addition, H(2)O(2) exposure resulted in cell shrinkage and chromatin condensation without nuclear fragmentation, indicating that H(2)O(2) stimulates a pyknotic cell death. Further analysis of AIF-transfected cells clearly demonstrated that nuclear translocation of AIF is the most important event required for nuclear condensation, phosphatidyl serine translocation, and ultimately cell death in H(2)O(2)-exposed cells. Furthermore, ATP was rapidly and severely depleted in cells exposed to H(2)O(2) generated by glucose oxidase but not by H(2)O(2) added as a bolus. Suppression of the H(2)O(2)-mediated ATP depletion by 3-aminobenzamide led to a significant increase of nuclear fragmentation in glucose oxidase-exposed cells. Collectively, these findings suggest that an acute energy reduction by H(2)O(2) causes caspase-independent and AIF-dependent cell death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1573-675X
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
796-808
pubmed:meshHeading
pubmed-meshheading:19418225-Adenosine Triphosphate, pubmed-meshheading:19418225-Apoptosis Inducing Factor, pubmed-meshheading:19418225-Caspases, pubmed-meshheading:19418225-Cell Death, pubmed-meshheading:19418225-Cell Line, Tumor, pubmed-meshheading:19418225-Cell Nucleus, pubmed-meshheading:19418225-Cell Survival, pubmed-meshheading:19418225-Chromatin, pubmed-meshheading:19418225-DNA Fragmentation, pubmed-meshheading:19418225-Enzyme Inhibitors, pubmed-meshheading:19418225-Glucose Oxidase, pubmed-meshheading:19418225-Humans, pubmed-meshheading:19418225-Hydrogen Peroxide, pubmed-meshheading:19418225-Intracellular Space, pubmed-meshheading:19418225-Membrane Potential, Mitochondrial, pubmed-meshheading:19418225-Mitochondria, pubmed-meshheading:19418225-Phosphatidylserines, pubmed-meshheading:19418225-Poly(ADP-ribose) Polymerases, pubmed-meshheading:19418225-Protein Transport, pubmed-meshheading:19418225-RNA, Small Interfering, pubmed-meshheading:19418225-Transfection
pubmed:year
2009
pubmed:articleTitle
Apoptosis-inducing factor plays a critical role in caspase-independent, pyknotic cell death in hydrogen peroxide-exposed cells.
pubmed:affiliation
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536-0001, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't