Molecular oxygen sensing: implications for visceral surgery

Langenbecks Arch Surg. 2012 Apr;397(4):603-10. doi: 10.1007/s00423-012-0930-z. Epub 2012 Mar 7.

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.

Publication types

  • Review

MeSH terms

  • Abdominal Neoplasms / blood supply
  • Abdominal Neoplasms / genetics
  • Adenosine Triphosphate / metabolism
  • Animals
  • Cell Death / genetics
  • Cell Death / physiology
  • Cell Hypoxia / genetics*
  • Cell Hypoxia / physiology*
  • Dioxygenases / genetics*
  • Dioxygenases / physiology*
  • Energy Metabolism / genetics
  • Energy Metabolism / physiology
  • Homeostasis / genetics
  • Homeostasis / physiology
  • Humans
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Immunity, Innate / genetics
  • Immunity, Innate / physiology
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / physiology*
  • Procollagen-Proline Dioxygenase / genetics*
  • Procollagen-Proline Dioxygenase / physiology*
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / genetics
  • Reperfusion Injury / physiopathology
  • Transcription Factors / genetics*
  • Transcription Factors / physiology*
  • Viscera / blood supply*
  • Viscera / surgery*

Substances

  • Nuclear Proteins
  • Reactive Oxygen Species
  • Transcription Factors
  • Adenosine Triphosphate
  • Dioxygenases
  • EGLN1 protein, human
  • Procollagen-Proline Dioxygenase
  • EGLN2 protein, human
  • EGLN3 protein, human
  • Hypoxia-Inducible Factor-Proline Dioxygenases