PARG activity mediates intestinal injury induced by splanchnic artery occlusion and reperfusion

Salvatore Cuzzocrea, Rosanna Di Paola, Emanuela Mazzon, Ulrich Cortes, Tiziana Genovese, Carmelo Muià, Weixing Li, Weizheng Xu, Jia He Li, Jie Zhang, Zhao Qi Wang

Research output: Contribution to journalArticlepeer-review

Abstract

Poly (ABP-ribosyl)ation, an early post-translational modification in response to DNA damage, is catalyzed by poly (ADP-ribose) polymerase (PARP-1) and caiabolized by poly(ABP-ribose) glycohydrolase (PARG). The aim of this study was to investigate the role of PARG on the modulation of the inflammatory response caused by splanchnic ischemia and reperfusion. SAO shock in rats and wild-type (WT) mice was associated with a significant neutrophil infiltration in the ileum and production of tumor necrosis factor-α (TNF-α). Reperfused ileum tissue sections from SAO-shocked WT mice and rats showed positive staining for P-selectin and ICAM-1 localized mainly in the vascular endothelial cells. Genetic disruption of the PARG gene in mice or pharmacological inhibition of PARG by PARG inhibitors significantly improved the histological status of the reperfused tissues associated with reduced expression of P-selectin and ICAM-1, neutrophil infiltration into the reperfused intestine, and TNF-α production. These results suggest that PARG activity modulates the inflammatory response in ischemia/reperfusion and participates in end (target) organ damage under these conditions.

Original languageEnglish (US)
Pages (from-to)558-566
Number of pages9
JournalFASEB Journal
Volume19
Issue number6
DOIs
StatePublished - Apr 2005
Externally publishedYes

Keywords

  • Ischemia and reperfusion
  • Neutrophil infiltration
  • Organ injury
  • PARG inhibitor
  • SAO shock

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

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