Linked Life Data

19931551

Source:http://linkedlifedata.com/resource/pubmed/id/19931551

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-2-9
pubmed:abstractText
It has been recently shown that acute acetaminophen toxicity results in endoplasmic reticulum redox stress and an increase in cells with apoptotic phenotype in liver. Since activation of effector caspases was absent, the relevance of caspase-independent mechanisms in acetaminophen-induced programmed cell death was investigated. BGP-15, a drug with known protective actions in conditions involving redox imbalance, has been co-administered with a single sublethal dose of acetaminophen. Proapoptotic events and outcome of the injury were investigated. ER redox alterations and early ER-stress-related signaling events induced by acetaminophen, such as ER glutathione depletion, phosphorylation of eIF2alpha and JNK and induction of the transcription factor GADD153, were not counteracted by co-treatment with BGP-15. However, BGP-15 prevented AIF mitochondria-to-nucleus translocation and mitochondrial depolarization. BGP-15 co-treatment attenuated the rate of acetaminophen-induced cell death as assessed by apoptotic index and enzyme serum release. These results reaffirm that acute acetaminophen toxicity involves oxidative stress-induced caspase-independent cell death. In addition, pharmacological inhibition of AIF translocation may effectively protect against or at least delay acetaminophen-induced programmed cell death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1096-0333
pubmed:author
pubmed:copyrightInfo
Copyright 2009 Elsevier Inc. All rights reserved.
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
243
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
96-103
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury.
pubmed:affiliation
Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, HAS Pathobiochemistry Research Group, H-1444 Budapest POB 260, Hungary.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't