Linked Life Data

9096604

Source:http://linkedlifedata.com/resource/pubmed/id/9096604

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-5-1
pubmed:abstractText
Although ceramide signaling pathways have been implicated in cell death, neither their role in hepatocellular death nor the cellular mechanisms mediating ceramide-induced cell death are known. The mitochondrial membrane permeability transition (MMPT) has been proposed as a common final pathway in cell death. Thus the aims of our study were to determine if ceramides cause hepatocellular death by necrosis and not apoptosis as confirmed by morphology and the absence of internucleosomal DNA cleavage. Ceramide-mediated hepatocyte necrosis was acyl chain-length, concentration, and time-dependent. Ceramides induced cell necrosis was associated with adenosine triphosphate (ATP) depletion and mitochondrial depolarization suggesting that ceramides caused mitochondrial dysfunction. In isolated mitochondria, ceramides induced the cyclosporine A-sensitive MMPT in an acyl chain-length and concentration dependent manner. Ceramide toxicity was specific as the less potent dihydro form did not induce cell necrosis, significant ATP depletion, mitochondrial depolarization nor the MMPT. In conclusion, ceramide induced cell death is acyl-chain length dependent and mediated by the MMPT. These data show for the first time that ceramide acts as a mediator of hepatocyte necrosis by causing mitochondrial failure.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0270-9139
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
958-63
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1997
pubmed:articleTitle
Ceramide induces hepatocyte cell death through disruption of mitochondrial function in the rat.
pubmed:affiliation
Center for Basic Research in Digestive Diseases, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't