Helicobacter pylori activation of PARP-1: usurping a versatile regulator of host cellular health

Gut Microbes. 2010 Nov-Dec;1(6):373-8. doi: 10.4161/gmic.1.6.13572.

Abstract

Chronic infection of the human stomach by Helicobacter pylori is an important risk factor for gastric cancer. H. pylori produces a cache of virulence factors that promote colonization and persistence, which, in turn, contributes to a robust inflammatory response at the host-pathogen interface. Recently, we reported that H. pylori activates the abundant nuclear regulator poly(ADP-ribose) polymerase (PARP)-1, resulting in the production of the catabolite poly(ADP-ribose) (PAR). PARP-1 is emerging as a key player in establishing homeostasis at the host-pathogen interface. In this article, we summarize the discovery of H. pylori-dependent PARP-1 activation, and discuss potential roles for PARP-1 in H. pylori-mediated gastric disease. In light of the remarkable successes that have reported for treating inflammatory disorders and cancers with PARP-1 inhibitors, we discuss the prospects of targeting PARP-1 for treatment of H. pylori-associated gastric disease.

Keywords: Helicobacter pylori; PARP-1; activation; apoptosis; cancer; inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Helicobacter Infections / immunology*
  • Helicobacter Infections / microbiology
  • Helicobacter Infections / pathology*
  • Helicobacter pylori / immunology*
  • Helicobacter pylori / pathogenicity*
  • Host-Pathogen Interactions*
  • Humans
  • Poly (ADP-Ribose) Polymerase-1
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism*

Substances

  • Poly Adenosine Diphosphate Ribose
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases