Linked Life Data

9563654

Source:http://linkedlifedata.com/resource/pubmed/id/9563654

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-5-7
pubmed:abstractText
Apoptosis is a morphologically and biochemically distinct form of cell death which can be triggered by a variety of extracellular agents both during normal developments and in adult pathological states. However, the molecular mechanism of apoptotic cell death due to hypoxia has not been clearly elucidated. In this study, we investigated critical factors involved in hypoxia-induced apoptosis using HepG2, a human hepatocellular carcinoma cell line, as an experimental model. We found that 24 h of exposure of HepG2 cells to hypoxia induced apoptosis, for which de novo protein synthesis was required. Apoptosis was demonstrated by DNA fragmentation and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. Hypoxia-induced apoptosis was associated with a marked induction of c-jun and c-fos messenger RNAs. Electromobility shift assay showed the increased DNA binding activity of AP-1 during hypoxia, suggesting that AP-1 may be involved in the induction of cell death by acting as a transcriptional regulator. A purine analogue, 6-thioguanine (6-TG), significantly blocked the induction of apoptosis by hypoxia. Moreover, the inductive effect of hypoxia on c-jun expression was also inhibited by 6-TG, whereas the levels of c-fos mRNA and its protein were rather strongly increased. Iodoacetamide (IAA), a non-specific inhibitor of ICE family proteases, also has an inhibitory effect on hypoxia-induced apoptosis. These results suggest that the 6-TG-sensitive protein kinase(s)-dependent signaling pathway may be involved in the apoptotic response of HepG2 cells exposed to hypoxia by increasing the level of c-jun and c-fos and the activity of AP-1 and/or by activating ICE family protease(s).
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0304-3835
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
126
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
97-104
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Hypoxia-induced apoptosis in human hepatocellular carcinoma cells: a possible involvement of the 6-TG-sensitive protein kinase(s)-dependent signaling pathway.
pubmed:affiliation
Department of Molecular Biology, Pusan National University, South Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't