Type

Journal Article

Authors

Cormac T Taylor
Eoin P Cummins
Alex Von Kriegsheim
Glen Doherty
Peter Carmeliet
Myriam Baes
Ulrike Bruning
Peter Fraisl
Mario C Manresa
Craig Slattery
and 11 others

Subjects

Biochemistry

Topics
prolyl hydroxylase hif 1 hypoxia inducible factor hif nf kappab nf b anti apoptotic transcription factors pre clinical

Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-κB-dependent manner. (2016)

Abstract Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1 confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) and nuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, we investigated the underlying mechanism(s) in hepatocytes. Basal NF-κB activity was elevated in PHD1(-/-) hepatocytes compared to wild type controls. ChIP-seq analysis confirmed enhanced binding of NF-κB to chromatin in regions proximal to the promoters of genes involved in the regulation of apoptosis. Inhibition of NF-κB (but not knock-out of HIF-1 or HIF-2) reversed the anti-apoptotic effects of pharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to altered expression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides new information relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that has been reported in pre-clinical models of intestinal and hepatic disease.
Collections Ireland -> University College Dublin -> PubMed

Full list of authors on original publication

Cormac T Taylor, Eoin P Cummins, Alex Von Kriegsheim, Glen Doherty, Peter Carmeliet, Myriam Baes, Ulrike Bruning, Peter Fraisl, Mario C Manresa, Craig Slattery and 11 others

Experts in our system

1
Cormac T. Taylor
University College Dublin
Total Publications: 110
 
2
Eoin P. Cummins
University College Dublin
Total Publications: 53
 
3
Alex Von Kriegsheim
University College Dublin
Total Publications: 19
 
4
Glen A Doherty
University College Dublin
Total Publications: 57
 
5
Ulrike Bruning
University College Dublin
Total Publications: 10
 
6
Mario C Manresa
University College Dublin
Total Publications: 8
 
7
Craig Slattery
University College Dublin
Total Publications: 27