Linked Life Data

19817749

Source:http://linkedlifedata.com/resource/pubmed/id/19817749

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-2-23
pubmed:abstractText
The hypoxia-inducible factor (HIF) is the master regulator for oxygen-dependent gene expression. The HIF signal transduction pathway can be manipulated by inhibiting the activity of the HIFalpha-regulating prolyl-4-hydroxylase domain (PHD) enzymes. The consequence of inhibiting the PHD activity for chemoresistance was studied. Inhibiting the PHD activity with the 2-oxoglutarate analog dimethyloxaloylglycine (DMOG) results in increased chemoresistance towards etoposide but not carboplatin in HeLa cells. Evidence for an etoposide-specific resistance, which develops as a consequence of inhibiting the PHD activity, was further supported in a tetracycline-inducible PHD2 knockdown HeLa cell model. The etoposide-resistance was mediated by HIF-1alpha as shown in mouse embryonic fibroblast HIF-1alpha(+/+) and HIF-1alpha(-/-) cells. Decreased cellular cytotoxicity after etoposide treatment inversely correlated with a dimethyloxaloylglycine (DMOG)-inducible, HIF-1alpha-dependent enhanced MDR-1 expression and efflux activity as determined by RT-PCR, immunoblots, and with the fluorescent dye DiOC2. Taken together, our data indicate that PHD inhibitors might increase chemoresistance of tumor cells in a HIF-1-dependent manner.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1349-7006
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
129-36
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Increased chemoresistance induced by inhibition of HIF-prolyl-hydroxylase domain enzymes.
pubmed:affiliation
Department of Cardiovascular Physiology, Georg August University Göttingen, Göttingen, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't