Linked Life Data

11516165

Source:http://linkedlifedata.com/resource/pubmed/id/11516165

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-8-22
pubmed:abstractText
Mitochondrial electron transport inhibitors induced two distinct pathways for acute cell death: lipid peroxidation-dependent and -independent in isolated rat hepatocytes. The toxic effects of mitochondrial complex I and II inhibitors, rotenone (ROT) and thenoyltrifluoroacetone (TTFA), respectively, were dependent on oxidative stress and lipid peroxidation, while cell death induced by inhibitors of complexes III and IV, antimycin A (AA) and cyanide (CN), respectively, was caused by MMP collapse and loss of cellular ATP. Accordingly, cellular and mitochondrial antioxidant depletion or supplementation, in general, resulted in a dramatic potentiation or prevention, respectively, of toxic injury induced by complex I and II inhibitors, with little or no effect on complex III and IV inhibitor-induced toxicity. ROT-induced oxidative stress was prevented by the addition of d-alpha-tocopheryl succinate (TS) but surprisingly TS did not afford hepatocytes protection against TTFA-induced oxidative damage. TS treatment prevented ROT-induced mitochondrial lipid hydroperoxide formation but had no effect on the loss of mitochondrial GSH or cellular ATP, suggesting a mitochondrial lipid peroxidation-mediated mechanism for ROT-induced acute cell death. In contrast, only fructose treatment provided excellent cytoprotection against AA- and CN-induced toxicity. Our findings indicate that complex III and IV inhibitors cause a rapid and severe depletion of cellular ATP content resulting in acute cell death that is dependent on cellular energy impairment but not lipid peroxidation. In contrast, inhibitors of mitochondrial complex I or II moderately deplete cellular ATP levels and thus cause acute cell death via a lipid peroxidation pathway.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0003-9861
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
393
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
87-96
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Mitochondrial electron transport inhibitors cause lipid peroxidation-dependent and -independent cell death: protective role of antioxidants.
pubmed:affiliation
Department of Pharmaceutical Sciences, Washington State University, Pullman, Washington 99164-6534, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't