Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-kB-dependent manner

Susan F Fitzpatrick, Zsolt Fábián, Bettina Schaible, Colin R Lenihan, Thomas Schwarzl, Javier Rodriguez, Xingnan Zheng, Zongwei Li, Murtaza M Tambuwala, Desmond G Higgins, Yvonne O'Meara, Craig Slattery, Mario C. Manresa, Peter Fraisl, Ulrike Bruning, Myriam Baes, Peter Carmeliet, Glen Doherty, Alex von Kriegsheim

Research output: Contribution to journalArticle

17 Citations (Scopus)
34 Downloads (Pure)


Hepatocyte death is an important contributing factor in a number of diseases of the liver. PHD1confers hypoxic sensitivity upon transcription factors including the hypoxia inducible factor (HIF) andnuclear factor-kappaB (NF-κB). Reduced PHD1 activity is linked to decreased apoptosis. Here, weinvestigated 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 ofpharmacologic hydroxylase inhibition. We hypothesize that PHD1 inhibition leads to alteredexpression of NF-κB-dependent genes resulting in reduced apoptosis. This study provides newinformation relating to the possible mechanism of therapeutic action of hydroxylase inhibitors that hasbeen reported in pre-clinical models of intestinal and hepatic disease.
Original languageEnglish
Pages (from-to)579-586
JournalBiochemical and Biophysical Research Communications
Issue number3
Early online date27 Apr 2016
Publication statusE-pub ahead of print - 27 Apr 2016


  • Prolyl hydroxylase
  • NF-κB
  • Apoptosis
  • Hypoxia

Fingerprint Dive into the research topics of 'Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-kB-dependent manner'. Together they form a unique fingerprint.

  • Cite this

    Fitzpatrick, S. F., Fábián, Z., Schaible, B., Lenihan, C. R., Schwarzl, T., Rodriguez, J., Zheng, X., Li, Z., Tambuwala, M. M., Higgins, D. G., O'Meara, Y., Slattery, C., Manresa, M. C., Fraisl, P., Bruning, U., Baes, M., Carmeliet, P., Doherty, G., & Kriegsheim, A. V. (2016). Prolyl hydroxylase-1 regulates hepatocyte apoptosis in an NF-kB-dependent manner. Biochemical and Biophysical Research Communications, 474(3), 579-586.