Judit Kiss1, Johanna Kirchberg, Martin Schneider. 1. Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Abstract
BACKGROUND: Since mammalian cells rely on the availability of oxygen, they have devised mechanisms to sense environmental oxygen tension, and to efficiently counteract oxygen deprivation (hypoxia). These adaptive responses to hypoxia are essentially mediated by hypoxia inducible transcription factors (HIFs). Three HIF prolyl hydroxylase enzymes (PHD1, PHD2 and PHD3) function as oxygen sensing enzymes, which regulate the activity of HIFs in normoxic and hypoxic conditions. Many of the compensatory functions exerted by the PHD-HIF system are of immediate surgical relevance since they regulate the biological response of ischemic tissues following ligation of blood vessels, of oxygen-deprived inflamed tissues, and of tumors outgrowing their vascular supply. PURPOSE: Here, we outline specific functions of PHD enzymes in surgically relevant pathological conditions, and discuss how these functions might be exploited in order to support the treatment of surgically relevant diseases.
BACKGROUND: Since mammalian cells rely on the availability of oxygen, they have devised mechanisms to sense environmental oxygen tension, and to efficiently counteract oxygen deprivation (hypoxia). These adaptive responses to hypoxia are essentially mediated by hypoxia inducible transcription factors (HIFs). Three HIF prolyl hydroxylase enzymes (PHD1, PHD2 and PHD3) function as oxygen sensing enzymes, which regulate the activity of HIFs in normoxic and hypoxic conditions. Many of the compensatory functions exerted by the PHD-HIF system are of immediate surgical relevance since they regulate the biological response of ischemic tissues following ligation of blood vessels, of oxygen-deprived inflamed tissues, and of tumors outgrowing their vascular supply. PURPOSE: Here, we outline specific functions of PHD enzymes in surgically relevant pathological conditions, and discuss how these functions might be exploited in order to support the treatment of surgically relevant diseases.
Authors: Eoin P Cummins; Edurne Berra; Katrina M Comerford; Amandine Ginouves; Kathleen T Fitzgerald; Fergal Seeballuck; Catherine Godson; Jens E Nielsen; Paul Moynagh; Jacques Pouyssegur; Cormac T Taylor Journal: Proc Natl Acad Sci U S A Date: 2006-11-17 Impact factor: 11.205
Authors: W M Bernhardt; U Gottmann; F Doyon; B Buchholz; V Campean; J Schödel; A Reisenbuechler; S Klaus; M Arend; L Flippin; C Willam; M S Wiesener; B Yard; C Warnecke; K-U Eckardt Journal: Proc Natl Acad Sci U S A Date: 2009-11-23 Impact factor: 11.205
Authors: Martin Mollenhauer; Judit Kiss; Johanna Dudda; Johanna Kirchberg; Nuh Rahbari; Praveen Radhakrishnan; Thomas Niemietz; Vanessa Rausch; Jürgen Weitz; Martin Schneider Journal: Langenbecks Arch Surg Date: 2012-09-11 Impact factor: 3.445
Authors: Jonathan Michael Harnoss; Moritz Johannes Strowitzki; Praveen Radhakrishnan; Lisa Katharina Platzer; Julian Camill Harnoss; Thomas Hank; Jun Cai; Alexis Ulrich; Martin Schneider Journal: Hypoxia (Auckl) Date: 2015-01-30